Data were derived from a longitudinal study of female twins in Missouri. The sample was composed of 3,532 twins (13.6% African-American [AA], 86.4% European-American [EA]), who participated in the fourth wave of data collection and reported consumption of at least 1 alcoholic drink over the lifetime. Mean age at Wave 4 was 21.7 (range = 18 to 29) years. Twin modeling was conducted to estimate the relative contributions of additive genetic (A), shared environmental (C), and unique environmental (E) factors to variation in age at first drink and problem alcohol use and the cross-phenotype overlap in these influences.

Early initiation of alcohol use predicted problem use in EA but not AA women. Separate AA and EA twin models produced substantially different estimates (but not statistically different models) of the relative contributions of A and C to problem alcohol use but similar genetic correlations between the phenotypes. Whereas 33% of the variance in the EA model of problem use was attributed to C, no evidence for C was found in the AA model. Heritability estimates for problem alcohol use were 41% in the AA model, 21% in the EA model. Evidence for A and C were found in both AA and EA models of age at first drink, but the A estimate was higher in the EA than AA model (44% vs. 26%).

Findings are suggestive of distinctions between AA versus EA women in the relative contribution of genetic and environmental influences on the development of problem drinking.

Age- and sex-matched C57BL/6 mice were fed the Lieber-DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 8 weeks. Mice from both diet groups were exposed to combustion-derived PM (CDPM) for the final 2 weeks. AM number, maturation, and polarization status were assessed by flow cytometry. Noninvasive and invasive strategies were used to assess pulmonary function and correlated with histomorphological assessments of airway structure and matrix deposition.

Co-exposure to alcohol and CDPM decreased AM number and maturation status (CD11c expression), while increasing markers of M2 activation (interleukin [IL]-4Rα, Ym1, Fizz1 expression, and IL-10 and transforming growth factor [TGF]-β production). Changes in AM function were accompanied by decreased airway compliance and increased elastance. Altered lung function was attributable to elevated collagen content localized to the small airways and loss of alveolar integrity. Intranasal administration of neutralizing antibody to TGF-β during the CDPM exposure period improved changes in airway compliance and elastance, while reducing collagen content caused by co-exposure.

Combustion-derived PM inhalation causes enhanced disease severity in the alcoholic lung by stimulating the release of latent TGF-β stores in AMs. The combinatorial effect of elevated TGF-β, M2 polarization of AMs, and increased oxidative stress impairs pulmonary function by increasing airway collagen content and compromising alveolar integrity.

A total of 347 adolescents (N = 279 at follow-up) from special secondary education, a risk group for the development of substance use problems, participated in the study. Automatic approach tendencies were assessed with the alcohol-approach avoidance task, inhibition skills were assessed with the Stroop task, and alcohol used was measured using a self-report measure.

Zero-inflated Poisson analysis revealed a significant effect of automatic approach tendencies predicting alcohol use 6 months later, although only for adolescents with weaker inhibition skills.

Automatic approach tendencies predict future drinking behavior of young adolescents with relatively weak inhibition skills. The findings of the present study have important implications for alcohol interventions for adolescents. Results are discussed in terms of risk factors for the development of problematic alcohol use in young adolescents.

This study was based on linked population data between 2002 and 2005 using the New South Wales (NSW) Midwives Data Collection (MDC) and the NSW Admitted Patients Data Collection (APDC), Australia. The study subjects included primiparous mothers who were admitted to hospital in the period from the sixth month before pregnancy to 1 year after birth with at least 1 of the following diagnoses (ICD-10-AM): mental and behavioral disorders due to the use of alcohol (MBDA) (F10.0–10.9); toxic effects of alcohol (T51.0–51.9); maternal care for suspected damage to fetus from alcohol (O35.4); or alcohol rehabilitation (Z50.2).

A total of 175 new mothers had 287 hospital admissions with the principal or stay AUD diagnoses during the study period in NSW. Of the 287 admissions, 181 admissions (63.07%) were reported for an alcohol-related disorder as the principal diagnosis. The hospital admission rate for AUD was 1.76/1,000 person-years (PY) (95% CI: 1.45 to 2.07) during the 6 months prepregnancy. The rate decreased to 0.49/1,000 PY (95% CI: 0.36 to 0.63) during pregnancy and to 0.82/1,000 PY (95% CI: 0.67 to 0.97) in the first year after birth. Women who smoked during pregnancy, lived in a remote area and were younger than 25 years, were more likely to be admitted to hospital with AUD diagnoses. Women in the middle disadvantaged quintile and born in other countries were less likely to be admitted to hospital with AUD diagnoses.

Hospital admission for AUD decreased significantly in pregnancy and the first year postpartum compared to the prepregnancy period.

To test whether these or other CSS-17 QTLs conferred resistance to alcohol-induced liver injury and fibrosis, B6, A/J, CSS-17, and congenics 17C-1 and 17C-6 were either fed Lieber–DeCarli ethanol (EtOH)-containing diet or had carbon tetrachloride (CCl₄) administered chronically.

The congenic strain carrying Obrq15 showed resistance from alcohol-induced liver injury and liver fibrosis, whereas Obrq13 conferred susceptibility to liver fibrosis. From published deep sequencing data for chromosome 17 in the B6 and A/J strains, we identified candidate genes in Obrq13 and Obrq15 that contained single-nucleotide polymorphisms (SNPs) in the promoter region or within the gene itself. NADPH oxidase organizer 1 (Noxo1) and NLR family, CARD domain containing 4 (Nlrc4) showed altered hepatic gene expression in strains with the A/J allele at the end of the EtOH diet study and after CCl₄ treatment.

Aspects of the genetics for the progression of ASH are unique compared to NASH, suggesting that the molecular mechanisms for the progression of disease are at least partially distinct. Using these CSSs, we identified 2 candidate genes, Noxo1 and Nlrc4, which modulate genetic susceptibility in ASH.

The subjects were 83 otherwise healthy men who developed persistent sexual side effects associated with finasteride, despite the cessation of this medication for at least 3 months. Information from standardized interviews was collected regarding medical histories, sexual function, and alcohol consumption before and after finasteride use.

Of the 63 men who consumed at least 1 alcoholic beverage/wk prior to starting finasteride, 41 (65%) noted a decrease in their alcohol consumption after stopping finasteride. This reduction typically began before discontinuing finasteride. Twenty men (32%) reported no change in their alcohol consumption, and 2 men (3%) reported an increase in their alcohol consumption. For the 63 consumers of alcohol, the mean number (±SE) of alcoholic beverages/wk declined from 5.2 ± 0.7 before finasteride to 2.0 ± 0.3 after finasteride (p < 0.0001). A major study limitation is the lack of a comparison group.

In former male users of finasteride who developed persistent sexual side effects, 65% noticed a decline in their alcohol consumption as compared to baseline. This finding is consistent with finasteride's ability to modulate alcohol intake in rodents. Further research is needed on the central nervous system effects of finasteride in humans.

Using the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093), we examined differences in sociodemographic characteristics, psychiatric and medical comorbidities, clinical correlates, risk factors, and treatment-utilization patterns of men (N = 2,974) and women (N = 1,807) with lifetime AD.

Men with lifetime AD were more likely than women to be diagnosed with any substance use disorder and antisocial personality disorder, whereas women were more likely to have mood and anxiety disorders. After adjusting for sociodemographic characteristics and gender differences in psychiatric comorbidity in the general population, AD was associated with externalizing disorders and any mood disorder among women only. Men with AD met more criteria, had longer episodes, and were younger at the age of first drink. There were no gender differences in remission rates. Women with AD were more likely to have a family and a spouse with history of alcohol use disorders. Treatment rates were low for both genders, and women were more likely to report social stigmatization as a treatment barrier.

There are important gender differences in the psychiatric comorbidities, risk factors, clinical characteristics, and treatment-utilization patterns among individuals with lifetime AD.

Acoustic startle and PPI of the acoustic startle were tested in 37 adult rhesus monkeys (Macaca mulatta) from 4 experimental conditions: (i) moderate-level prenatal alcohol-exposed, (ii) prenatally stressed, (iii) moderate-level prenatal alcohol-exposed + prenatally stressed, and (iv) sucrose controls.

Prenatal alcohol-exposed monkeys showed a higher magnitude of acoustic startle response and disrupted PPI compared with monkeys not exposed to alcohol prenatally. Monkeys in all conditions showed higher hypothalamic–pituitary–adrenocortical (HPA) axis responses after undergoing the startle procedure, but HPA responses were unrelated to startle response magnitude, latency, or PPI.

Finding altered PPI in monkeys prenatally exposed to a moderate dose of alcohol suggests that reduced sensorimotor gating is 1 effect of prenatal alcohol exposure. Because reduced sensorimotor gating is observed in many neuropsychiatric disorders, sensorimotor gating deficits could be an aspect of the comorbidity between fetal alcohol spectrum disorder and mental health conditions.

We utilized a mouse model of binge drinking known as drinking in the dark (DID), where C57BL/6J mice drink approximately 6 g/kg in 4 hours and achieve blood EtOH concentrations of approximately 100 mg/dl, which is equivalent to binge drinking in humans. We used ex vivo whole-cell recordings from putative VTA dopamine (DA) neurons to examine CRF regulation of NMDA receptor (NMDAR) currents. We also examined the impact of CRF receptor antagonist injection in the VTA on binge EtOH intake.

Ex vivo whole-cell recordings from putative VTA DA neurons showed enhanced CRF-mediated potentiation of NMDAR currents in juvenile mice that consumed EtOH in the DID procedure. CRF-induced potentiation of NMDAR currents in EtOH-drinking mice was blocked by administration of CP-154,526 (3 μM), a selective CRF₁ receptor antagonist. Furthermore, intra-VTA infusion of CP-154,526 (1 μg) significantly reduced binge EtOH consumption in adult mice. These results were not due to alterations of VTA NMDAR number or function, suggesting that binge drinking may enhance signaling through VTA CRF₁ receptors onto NMDARs.

Altered CRF₁ receptor-mediated signaling in the VTA promotes binge-like EtOH consumption in mice, which supports the idea that CRF₁ receptors may therefore be a promising pharmacological target for reducing binge drinking in humans.

Pregnant Sprague–Dawley rats received the following diets: control (C; ad libitum standard laboratory chow), nutritional control pair-fed (PF), ethanol (EtOH), or an EtOH diet supplemented with 0.3, 1.5, or 7.5 mg thyroxine (T4)/l in the diet. Social behavior and memory were tested in the adult offspring. Plasma total T4, free T3 (fT3), and thyroid-stimulating hormone (TSH) levels were measured. Hippocampal expression of Gabrb3, Ube3a, Nr2b, Rasgrf1, and Dio3 were measured by RT-qPCR and protein levels of Mecp2 and Slc25a12 by Western blotting.

Adult male offspring of EtOH dams showed elevated fT3 and low TSH levels. Adult male, but not female, offspring of EtOH dams exhibited social behavior and memory deficits. Expression of autism candidates, Gabrb3, Ube3a, Mecp2, and Slc25a12, was significantly increased in the hippocampus of male offspring of EtOH dams. Hippocampal Nr2b and Dio3 were also increased, while Rasgrf1 was decreased in the same population. Peripheral thyroid function, social behavioral deficits, and altered expression of the above genes were normalized by simultaneous administration of 0.3 mg/l T4 in the EtOH diet.

Our data suggest that social interaction deficits of FASD share molecular mechanism with ASD by showing altered hippocampal expression of several ASD candidate genes. Social interaction deficits as well as the gene expression changes in the offspring of EtOH-consuming dams can be reversed by low dose of thyroid hormone supplementation to the mothers.

Wild-type (WT) and the iron-loaded Hfe-null (Hfe^−/−) mice were fed chow (CC), a AIN-93G standard control (SC), or a corn oil–modified, AIN-93G-based (CO) diet with or without the addition of 20% ethanol (EtOH) in the drinking water for 8 weeks and assessed for liver injury.

WT mice on CC, SC, and CO diets had no liver injury, although mild steatosis developed in the SC and CO groups. The addition of EtOH resulted in mild steatohepatitis in WT mice fed SC but not those on a CO diet. EtOH administration in Hfe^−/− animals on the CC and SC diets caused marked oxidative stress, inflammatory activity, and subsinusoidal and portal–portal tract linkage fibrosis with significant up-regulation of genes involved in cellular stress signaling and fibrogenic pathways. These effects were abrogated in the CO-fed mice, despite elevated serum EtOH levels and hepatic iron concentrations, reduced hepatic glutathione and mitochondrial superoxide dismutase activities. Feeding with the CO diet led to increased hepatic glutathione peroxidase and catalase activities and attenuated alcohol-induced hepatic steatosis in the Hfe^−/− animals. Iron and EtOH feeding markedly reduced p-STAT3 and p-AMPK protein levels, but this effect was significantly attenuated when a CO diet was consumed.

A CO-based diet is protective against combined EtOH- and iron-induced liver toxicity, likely via attenuation of hepatic steatosis and oxidative stress and may have a role in the prevention of fibrosis development in chronic liver disease.

A cross-sectional survey compared 2 strategies for recruiting disadvantaged men to a study on alcohol consumption: recruitment through general practice (GP) registers and through a community outreach strategy, respondent-driven sampling (RDS). Men aged 25 to 44 years were recruited from deprived areas in the community. The entry criterion was binge drinking (≥8 units in a single session) at least twice in the previous 4 weeks. Demographic characteristics, total consumption of alcohol, frequency of binge drinking (≥8 units in a session), and heavy binge drinking (≥16 units in a session) were measured.

Men recruited by RDS drank more than twice as much as the men recruited through GP (137 units in the previous 30 days compared with 62 units; p = 0.003). They also had many more binge drinking days: more than half (57%) of men from RDS had 6 or more binge drinking days in the previous 30 days, whereas only 16% of the GP sample had 6 or more binge drinking days (p = 0.001). Many more men recruited by RDS (37% vs. 5%; p = 0.002) had more than 5 very heavy drinking sessions in the previous month (≥16 units in a session). The RDS group also had fewer alcohol-free days.

The 2 sampling strategies recruited different types of drinkers. The men recruited through RDS were much more likely to engage in frequent harmful drinking. The results indicate that the 2 methods recruit different samples of disadvantaged men. Intervention studies that are only conducted through primary care may miss many harmful drinkers.

Subjects included were 252 participants in monitoring with the Alabama Physician Health Program. All subjects testing positive for EtG and/or ethyl sulfate (EtS) who denied drinking after routine supportive confrontation were subject to information about PEth testing. If they still denied drinking, PEth testing was performed and the result communicated. EtG, EtS, and PEth testing was performed in a commercial laboratory using liquid chromatography tandem mass spectrometry methods.

Of a total of 18 subjects who tested positive for EtG and/or EtS, 10 denied drinking. Of the 7 who denied drinking after PEth explanation, in 5 cases, their claim was supported by a negative PEth result. In 2 cases, a positive PEth result was in contrast to their claim.

PEth results in combination with previous low positive EtG/EtS results allow differentiating between innocent/extraneous exposure and drinking. Negative PEth testing following low positive EtG/EtS results helps to further elucidate the findings and support the claim of the patient of recent alcohol abstinence. Positive PEth testing following positive EtG/EtS results confirms recent drinking.

In study one, alcohol-experienced P rats that had been drinking alcohol for 2 h/d for several months were treated daily with prazosin (0, 0.5, 1.0, or 2.0 mg/kg body weight [BW]) for 7 weeks. In study two, alcohol-naïve P rats were treated daily with prazosin (0, 1.0, or 2.0 mg/kg BW) for 2 weeks prior to, or concomitantly with, the initiation of alcohol access and throughout 3 weeks of alcohol availability. Prazosin treatment and alcohol access were then discontinued for 2 weeks followed by reinstatement of alcohol access without prazosin treatment for 4 weeks, followed by resumption of daily prazosin treatment (2.0 mg/kg BW) for 3 weeks.

Prazosin reduced alcohol drinking throughout 7 weeks of treatment in P rats accustomed to drinking alcohol. Following termination of prazosin treatment, alcohol drinking slowly returned to pretreatment baseline. Reduced alcohol intake was accompanied by increased water intake. In alcohol-naïve P rats, prazosin administration prior to the first opportunity to drink alcohol and throughout 3 weeks of alcohol access retarded acquisition of alcohol drinking and reduced the amount of alcohol consumed. When prazosin was administered concomitantly with the first opportunity to drink alcohol, it abolished acquisition of alcohol drinking. Discontinuation of prazosin treatment allowed expression of a genetic predisposition toward high alcohol drinking to gradually emerge. Prazosin retained the ability to reduce alcohol intake with repeated treatments.

Prazosin decreased alcohol drinking during prolonged treatment and may be useful for treating alcoholism and alcohol-use disorders. Prazosin may also be useful for deterring the initiation of drinking in individuals with a family history of alcoholism.

Hela cells were transfected with Epac1-camps, dopamine (DA) receptor D_1a, and 1 isoform of AC (AC7 or AC3). Fluorescent images were captured using a specific filter set for cyan fluorescent protein (CFP), yellow fluorescent protein (YFP), and FRET, respectively, and FRET intensity was calculated on a pixel-by-pixel basis to examine changes in cAMP.

During 2-minute stimulation with DA, the cytoplasmic cAMP level quickly increased and then decreased to a plateau, where the cAMP level was higher than the level prior to stimulation with DA. EtOH concentration dependently increased cytoplasmic cAMP in cells transfected with AC7, while EtOH did not have effect on cells transfected with AC3. Similar trends were observed for cAMP at the plasma membrane and in the nucleus during 2-minute stimulation with DA. Unexpectedly, when cells expressing AC7 were stimulated with DA or other Gs-coupled receptor's ligand plus EtOH for 5 seconds, EtOH reduced cAMP concentration.

These results suggest that EtOH has 2 opposing effects on the cAMP-generating system in an AC isoform-specific manner, the enhancing effect on AC activity and the short-lived inhibitory effect. Thus, EtOH may have a different effect on cAMP depending on not only AC isoform but also the duration of exposure.

We analyzed 6 biennial surveys (1999 to 2009) of individual-level youth alcohol use and related behaviors from state-based Youth Risk Behavior Surveys and corresponding years of state-level adult binge drinking prevalence from the Behavioral Risk Factor Surveillance System. We employed logistic regression with generalized estimating equations method to assess the extent to which state adult binge drinking predicted individual-level youth drinking outcomes and examined the role of alcohol taxes in that relationship.

Population-aggregate analyses based on 194 state-year strata showed a positive correlation between state adult binge drinking and youth binge drinking (Pearson r = 0.40, p < 0.01). For individual-level youth drinking outcomes, a 5 percentage point increase in binge drinking prevalence among adults was associated with a 12% relative increase in the odds of alcohol use (adjusted OR = 1.12, 95% CI: 1.08, 1.16). Taxes were strongly inversely related with adult and youth drinking measures, and the effect of tax on youth drinking was attenuated after controlling for adult binge drinking.

Both tax and adult binge drinking are strong predictors of youth drinking. Tax may affect youth drinking through its effect on adult alcohol consumption. Implementing effective alcohol policies to reduce excessive drinking in the general population is an important strategy to reduce youth drinking.

Pubertal stage at first drink (PSFD) was determined in N = 283 young adults (131 males, 152 females) from an epidemiological cohort study. At ages 19, 22, and 23 years, drinking behavior (number of drinking days, amount of alcohol consumed, hazardous drinking) was assessed using interview and questionnaire methods. Additionally, an animal study examined the effects of pubertal or adult ethanol (EtOH) exposure on voluntary EtOH consumption in later life in 20 male Wistar rats.

PSFD predicted drinking behavior in humans in early adulthood, indicating that individuals who had their first drink during puberty displayed elevated drinking levels compared to those with postpubertal drinking onset. These findings were corroborated by the animal study, in which rats that received free access to alcohol during the pubertal period were found to consume more alcohol as adults, compared to the control animals that first came into contact with alcohol during adulthood.

The results point to a significant role of stage of pubertal development at first contact with alcohol for the development of later drinking habits. Possible biological mechanisms and implications for prevention are discussed.

This study used a daily-level, academic-year-long, multisite sample to describe adherence to NIAAA daily (no more than 4 drinks per day for men, 3 drinks per day for women) and weekly (no more than 14 drinks per week for men, 7 drinks per week for women) drinking guidelines, and to test for sex differences and time effects. College students (n = 992; 58% female) reported daily drinking on a biweekly basis using web-based surveys throughout their first year of college.

Women exceeded weekly limits more frequently (15% of weeks [14 to 17%]) than men (12% [10 to 14%]). Women and men exceeded daily drinking limits similarly often (25 and 27%, respectively). In a generalized estimating equations analysis across all 18 biweekly assessments, adjusted for covariates and a linear trend over time, women were more likely to exceed weekly guidelines compared to men. Sex differences in exceeding daily limits were not significant. Over time, rates of exceeding limits declined for daily limits but only for men for weekly limits.

Female college students are more likely to exceed weekly alcohol intake limits than men. Furthermore, trends over time suggest that college students may be maturing out of heavy episodic drinking, but women may not mature out of harmful levels of weekly drinking. The observed disparity in risk for long-term health consequences may represent a missed opportunity for education and intervention.

Six alcohol ads selected for their likelihood of having code violations were rated by community and expert participants (N = 286). Quantitative rating scales were used to measure the content of alcohol advertisements based on alcohol industry self-regulatory guidelines. The community group participants represented vulnerability characteristics that industry codes were designed to protect (e.g., age <21); experts represented various health-related professions, including public health, human development, alcohol research, and mental health. Alcohol ads were rated on 2 occasions separated by 1 month. After completing Time 1 ratings, participants were randomized to receive feedback from 1 group or the other.

Findings indicate that (i) ratings at Time 2 had generally reduced variance, suggesting greater consensus after feedback, (ii) feedback from the expert group was more influential than that of the community group in developing group consensus, (iii) the expert group found significantly fewer violations than the community group, (iv) experts representing different professional backgrounds did not differ among themselves in the number of violations identified, and (v) a rating panel composed of at least 15 raters is sufficient to obtain reliable estimates of code violations.

The Delphi technique facilitates consensus development around code violations in alcohol ad content and may enhance the ability of regulatory agencies to monitor the content of alcoholic beverage advertising when combined with psychometric-based rating procedures.

Cross-sectional performances of never-smoking healthy comparison participants (nvsCOM; n = 39) and 1-month-abstinent, treatment-seeking, never-smoking (nvsALC; n = 30), former-smoking (fsALC; n = 21), and actively smoking (asALC; n = 68) ALC were compared on a comprehensive neurocognitive battery. Domains of functioning evaluated were cognitive efficiency, executive functions, fine motor skills, general intelligence, learning and memory, processing speed, visuospatial functions and working memory. Participants were between 26 and 71 years of age at the time of assessment.

asALC showed steeper age-related effects than nvsCOM on the domains of visuospatial learning, auditory-verbal memory, cognitive efficiency, executive functions, processing speed, and fine motor skills. In pairwise comparisons, fsALC and asALC performed more poorly than both nvsCOM and nvsALC on multiple domains; nvsCOM and nvsALC showed no significant differences. Domain scores for the ALC groups generally fell in the low-to-high-average range of functioning. A clinically significant level of impairment was apparent in only 25% of ALC participants on visuospatial learning, visuospatial memory, and fine motor skills domains. Measures of alcohol use or consumption were not significantly related to neurocognition in the ALC cohorts.

The age-related findings suggest that the combination of active chronic smoking and alcohol dependence in this 1-month-abstinent ALC cohort was associated with greater than normal age-related effects in multiple domains. In general, a low level of clinically significant impairment was observed in the alcohol-dependent participants. The findings from this study, in conjunction with previous research, strongly support smoking cessation interventions for those seeking treatment for alcohol and substance use disorders.

Suffolk ewes were mated and received intravenous infusions of saline or alcohol (1.75 g/kg) over 1 hour on 3 consecutive days per week followed by 4 days without treatment beginning on gestational day (GD) 109 and concluding on GD 132 (term = 147 days). The acidemia group was exposed to increased inspired fractional concentrations of CO₂ to closely mimic the alcohol-induced decreases in maternal arterial pH seen in the alcohol group.

Fetal femurs and tibias from the alcohol and acidemia groups were ~3 to 7% shorter in length compared with the control groups (p < 0.05). Three-point bending procedure demonstrated that fetal femoral ultimate strength (MPa) for the alcohol group was decreased (p < 0.05) by ~24 and 29%, while the acidemia group exhibited a similar decrease (p < 0.05) of ~32 and 37% compared with the normal control and saline control groups, respectively. Bone extrinsic and intrinsic mechanical properties including maximum breaking force (N) and normalized breaking force (N/kg) of fetal bones from the alcohol and acidemia groups were significantly decreased (p < 0.05) compared with both control groups.

We conclude that late gestational chronic binge alcohol exposure reduces growth and impairs functional properties of the fetal skeletal system and that the repeated episodes of alcohol-induced maternal acidemia may be at least partially responsible for these effects.

The current study extends this translational approach by testing the hypothesis that rehabilitation training involving 20 days of training on traversal of an obstacle course (complex motor learning) would ameliorate the deficits on classical conditioning of eyeblink responses produced by the neonatal alcohol exposure. We have previously shown that this training stimulates cerebellar synaptic plasticity and improves alcohol-induced deficits on motor coordination tasks.

The current studies found that rehabilitation training significantly attenuated alcohol-induced deficits in acquisition of eyeblink conditioning in females but not in males. These results are consistent with normalization of cerebellar-dependent learning, at least in alcohol-exposed females.

These findings extend previous studies in this model suggesting that rehabilitation of adolescents with FASD using training with complex motor learning tasks could be effective in ameliorating functional impairments associated with cerebellar damage. Eyeblink classical conditioning deficits are now well documented in children with FASD and could serve as an evaluation measure to continue to develop therapeutic interventions such as complex motor learning.

We conducted a retrospective cohort study of medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal using 2 administrative databases. The primary outcome was time to rehospitalization or death. Secondary outcomes included time to first emergency department or urgent care clinic visit in the subset of ICU survivors who were not rehospitalized. Cox proportional hazard models were adjusted for age, gender, race, homelessness, smoking, and payer source.

Of 1,178 patients discharged from the medical ICU over the study period, 468 (40%) were readmitted to the hospital and 54 (4%) died within 1 year. Schizophrenia (hazard ratio 2.23, 95% CI 1.57, 3.34, p < 0.001), anxiety disorder (hazard ratio 2.04, 95% CI 1.30, 3.32, p < 0.01), depression (hazard ratio 1.62, 95% CI 1.05, 2.40, p = 0.03), and Deyo comorbidity score ≥3 (hazard ratio 1.43, 95% CI 1.09, 1.89, p = 0.01) were significant predictors of time to death or first rehospitalization. Bipolar disorder was associated with time to first emergency department or urgent care clinic visit (hazard ratio 2.03, 95% CI 1.24, 3.62, p < 0.01) in the 656 patients who were alive and not rehospitalized within 1 year.

The presence of a psychiatric comorbidity is a significant predictor of multiple measures of unplanned healthcare utilization in medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal. This finding highlights the potential importance of targeting longitudinal multidisciplinary care to patients with a dual diagnosis.

We performed a cross-sectional multivariable analysis of the association between lifetime alcohol use and liver fibrosis in a longitudinal cohort of HIV-infected patients with alcohol problems. Liver fibrosis was estimated with 2 noninvasive indices, “FIB-4,” which includes platelets, liver enzymes, and age; and aspartate aminotransferase/platelet ratio index (“APRI”), which includes platelets and liver enzymes. FIB-4 <1.45 and APRI <0.5 defined the absence of liver fibrosis. FIB-4 >3.25 and APRI >1.5 defined advanced liver fibrosis. The main independent variable was lifetime alcohol consumption (<150 kg, 150 to 600 kg, >600 kg).

Subjects (n = 308) were 73% men, mean age 43 years, 49% with hepatitis C virus (HCV) infection, 60% on antiretroviral therapy, 49% with an HIV RNA load <1,000 copies/ml, and 18.7% with a CD4 count <200 cells/mm³. Forty-five percent had lifetime alcohol consumption >600 kg, 32.7% 150 to 600 kg, and 22.3% <150 kg; 33% had current heavy alcohol use, and 69% had >9 years of heavy episodic drinking. Sixty-one percent had absence of liver fibrosis and 10% had advanced liver fibrosis based on FIB-4. In logistic regression analyses, controlling for age, gender, HCV infection, and CD4 count, no association was detected between lifetime alcohol consumption and the absence of liver fibrosis (FIB-4 <1.45) (adjusted odds ratio [AOR] = 1.12 [95% CI: 0.25 to 2.52] for 150 to 600 kg vs. <150 kg; AOR = 1.11 [95% CI: 0.52 to 2.36] for >600 kg vs. <150 kg; global p = 0.95). Additionally, no association was detected between lifetime alcohol use and advanced liver fibrosis (FIB-4 >3.25). Results were similar using APRI, and among those with and without HCV infection.

In this cohort of HIV-infected patients with alcohol problems, we found no significant association between lifetime alcohol consumption and the absence of liver fibrosis or the presence of advanced liver fibrosis, suggesting that alcohol may be less important than other known factors that promote liver fibrosis in this population.

Male adult Swiss mice treated chronically with EtOH (2 g/kg, i.p., daily for 21 days) were classified as “EtOH_High” or “EtOH_Low” according to their locomotor activity after the 21st EtOH injection. A control group was similarly injected with saline. Temporal analysis of CB1R and CB2R immunoreactivity was performed in 3 different occasions: (i) at the end of chronic EtOH treatment, (ii) on the fifth day of EtOH withdrawal, and (iii) after EtOH challenge.

Overall, no differences were seen between experimental groups regarding the CB1R at the end of acquisition. However, there were decreases in CB2R in the prefrontal cortex and the hippocampus in EtOH_Low mice. On the fifth day of withdrawal, only EtOH_High mice presented increase in CB1R. Nonetheless, CB2R up-regulation was observed in both EtOH_High and EtOH_Low mice. EtOH challenge counteracted CB1R and CBR2 up-regulation, mainly in the EtOH_High, in structures related to emotionality, such as prefrontal cortex, ventral tegmental area, amygdala, striatum, and hippocampus.

There are different patterns of cannabinoid receptor expression during locomotor sensitization paradigm, at both temporal and behavioral perspectives. We hypothesize that CB2R down-regulation might be related to resilience to develop locomotor sensitization, while CB1R up-regulation relates to withdrawal aspects in sensitized mice.

Male C57BL/6J mice first experienced 0 to 10 four-day binge-like drinking episodes (3 days of rest between episodes). Beginning 24 hours after the final binge-like drinking session, mice were tested for anxiety-like behaviors (with elevated plus maze [EPM] and open-field locomotor activity tests), ataxia with the rotarod test, and sensitivity to handling-induced convulsions (HICs). One week later, mice began a 40-day 2-bottle (water vs. EtOH) voluntary consumption test with concentration ranging from 10 to 20% (v/v) EtOH.

A prior history of binge-like EtOH drinking significantly increased subsequent voluntary EtOH consumption and preference, effects most robust in groups that initially experienced 6 or 10 binge-like drinking episodes and completely absent in mice that experienced 1 binge-like drinking episode. Conversely, a history of binge-like EtOH drinking did not influence anxiety-like behaviors, ataxia, or HICs.

Excessive EtOH drinking stemming from DID procedures does not initially induce phenotypes consistent with a dependence-like state. However, the subsequent increases in voluntary EtOH consumption and preference that become more robust following repeated episodes of binge-like EtOH drinking may reflect the early stages of EtOH dependence, suggesting that DID procedures may be ideal for studying the transition to EtOH dependence.

Using data from the Pregnancy Risk Assessment Monitoring System from 2004 to 2008, 111,644 women who completed questions relating to periconceptional alcohol use and multivitamin supplement use were included in the study. This study explored associations between periconceptional alcohol use and multivitamin supplementation use. Weighted multivariable logistic regression was used to explore associations, adjusting for maternal education, maternal ethnicity, maternal age, household income, and parity.

During the periconceptional period, a dose-dependent association was found where women who consumed alcohol (≤3 drinks/wk, odds ratio [OR] = 0.76; 4 to 6 drinks/wk, OR = 0.60; 7 to 13 drinks/wk, OR = 0.49; ≥14 drinks/wk, OR = 0.39) and binged on alcohol (1 time, OR = 0.76; 2 to 3 times, OR = 0.66; 4 to 5 times, OR = 0.56; ≥6 times, OR = 0.50) were significantly less likely to take a multivitamin supplement compared with those that did not consume alcohol.

These findings emphasize the importance of periconceptional multivitamin supplement use, especially among alcohol-consuming women of childbearing age.

In the current set of studies, we examined in rats the effect of caffeine administration on alcohol drinking and intravenous (i.v.) self-administration of nicotine. In male alcohol-preferring (P) rats, caffeine (5, 10, and 20 mg/kg) or the saline vehicle was administered acutely either by subcutaneous (S.C.) injection or orally (PO) by gavage. In a chronic study, the effect of PO caffeine (5 and 20 mg/kg) on alcohol intake over a 10-day period was tested. In another experiment, the effect of acute PO administration of caffeine (20 mg/kg) or saline on saccharin intake (0.2% solution) was determined in P rats. Effects of 20 mg/kg caffeine on motor activity were also determined in P rats. Finally, the effects of acute PO caffeine administration on nicotine self-administration in Sprague–Dawley rats were also determined.

Both routes of administration of caffeine, S.C. and PO, caused a significant dose-related decrease in alcohol intake and preference during free access to alcohol and after 4-day deprivation of alcohol. However, the low dose of 5 mg/kg caffeine increased alcohol intake. Acute PO caffeine also reduced saccharin intake. Acute systemic administration of 20 mg/kg caffeine did not exert a significant effect on motor activity. In Sprague–Dawley rats trained to self-administer i.v. nicotine, acute PO administration of caffeine significantly increased self-administration of nicotine in a dose-related manner.

These results suggest that adenosine receptor systems may play a role in both alcohol and nicotine intake and deserve further study regarding these addictions.

This post hoc analysis of data from the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) included 26,546 U.S. adults who reported drinking in the past year and answered additional questions about their consumption, including Alcohol Use Disorders Identification Test—Consumption questionnaire (AUDIT-C) alcohol screening. Linear or logistic regression models and postestimation methods were used to estimate mean daily drinking, the number of endorsed alcohol use disorder (AUD) criteria (“AUD severity”), and the probability of alcohol dependence associated with each individual AUDIT-C score (1 to 12), after testing for effect modification by gender and age.

Among eligible past-year drinkers, mean daily drinking, AUD severity, and the probability of alcohol dependence increased exponentially across increasing AUDIT-C scores. Mean daily drinking ranged from < 0.1 to 18.0 drinks/d, AUD severity ranged from < 0.1 to 5.1 endorsed AUD criteria, and probability of alcohol dependence ranged from < 1 to 65% across scores 1 to 12. AUD severity increased more steeply across AUDIT-C scores among women than men. Both AUD severity and mean daily drinking increased more steeply across AUDIT-C scores among younger versus older age groups.

Results of this study could be used to estimate patient-specific consumption and severity based on age, gender, and alcohol screening score. This information could be integrated into electronic decision support systems to help providers estimate and provide feedback about patient-specific risks and identify those patients most likely to benefit from further diagnostic assessment.

CDT was assayed at the central laboratory of the Ghent University Hospital by capillary zone electrophoresis, measured on the Capillarys 2™ system and was expressed as a percentage of total serum transferrin (%CDT). Serum of chronic alcohol abusers was compared to nonheavy drinkers using agarose gel isoelectric focusing (IEF). Total β-HEX activity was assayed fluorimetrically following preparative IEF in 81 subjects. β-HEX isoforms were investigated and compared between nonheavy drinkers and heavy drinkers.

Agarose gel IEF shows additional cathodal bands in serum of chronic alcohol abusers. Mean total β-HEX activity between pH 6.8 and 7.7, designated as HEX-7, showed the highest correlation with %CDT (r = 0.70, p < 0.0001, n = 68). In a selected subgroup, where CDT could not be quantified (n = 13) because of an atypical electropherogram, HEX-7 was in concordance with either estimated %CDT value or liver enzyme activities.

In this proof-of-concept study, we introduce a novel approach to quantify β-HEX isoforms using preparative IEF and fluorimetry. A highly significant correlation of HEX-7 and %CDT has been found. Because of exclusion of the P isoform, HEX-7 could be a useful supplementary marker for detecting chronic alcohol abuse.

Admissions data from 1996 to 2010 were retrieved from the National Health Insurance Research Database (NHIRD) claims file and analyzed in this study. Data on 430,388 men and 34,874 women aged 15 or above who had an admission due to an AAD were collected. An interrupted time series analysis examining the effects of the implementation of alcohol tax policy on quarterly age- and sex-specific incidence rates of hospitalization for AADs was employed. The same method was also used to analyze hospitalizations for alcoholic liver disease.

The teen/adult groups all showed significant (p < 0.05) changes in the adjusted incidence rate of hospitalization (AIRH) for AADs and alcoholic liver disease in 2002. Men aged 15 to 64 years showed an abrupt decline in the rate of AADs (9.1%) and in the rate of alcoholic liver disease (10.3%). A 16% reduction in the AAD rate was found in teen/adult women after the alcohol tax increase. In contrast, a 17.4% increase in the same rate was seen in the first quarter of 2010 for this group. A similar pattern was presented for the AIRH for alcoholic liver disease among women. The effect of tax intervention was not significant among the elderly.

This study provides evidence that alcohol taxation in response to international trade liberalization has resulted in an immediate reduction of AADs in Taiwan. The policy of increasing alcohol tax rates may have favorable influences on the time trend for the rate of AADs, most notably among young and middle-aged men and women.

Between 1995 and 2010, 92 cirrhotic alcoholic patients underwent liver transplantation. Clinical evaluation and management of alcohol use in these patients was provided by psychiatrists with expertise in addiction medicine not affiliated to the liver transplant center before 2002 (n = 37; group A), or by the clinical staff of the AAU within the liver transplant center starting from 2002 (n = 55; group B).

Group B, as compared with group A, showed a significantly lower prevalence of alcohol recidivism (16.4 vs. 35.1%; p = 0.038) and a significantly lower mortality (14.5 vs. 37.8%; p = 0.01). Furthermore, an analysis of group B patients with either ≥6 or <6 months of alcohol abstinence before transplantation showed no difference in the rate of alcohol recidivism (21.1 vs. 15.4%; p = ns).

The presence of an AAU within a liver transplant center reduces the risk of alcohol recidivism after transplantation. A pretransplant abstinence period <6 months might be considered, at least in selected patients managed by an AAU.

High and low alcohol withdrawal mice (second replicate: high and low acute alcohol withdrawal [HAW-2/LAW-2]) were trained and tested in a Go/No-go task. Mice were administered 0.0, 0.5, 1.0, and 1.5 g/kg ethanol (EtOH) on 3 occasions according to an incomplete Latin Square. A separate cohort of C57BL/6J (B6) and DBA/2J (D2) mice (the progenitor strains for HAW-2/LAW-2 mice) underwent the same protocol, using the same EtOH doses.

HAW-2 and LAW-2 mice did not differ in behavioral inhibition at baseline, although LAW-2 mice did have higher overall levels of responding in the task. EtOH did not alter behavioral inhibition in these mice. However, it did decrease responses to the Go cue, and this effect was greater in HAW-2 mice than in LAW-2 mice. D2 mice had lower behavioral inhibition than B6 mice at baseline, and EtOH slightly decreased behavioral inhibition in both strains.

The findings with D2 and B6 mice generally fit with the existing literature. However, the lack of a difference in behavioral inhibition between HAW-2 and LAW-2 mice was unexpected, as well as the absence of any effect of these doses of EtOH on behavioral inhibition in these mice. Nonetheless, the findings do suggest that selectively breeding for high or low withdrawal to acute alcohol can lead to differences in operant behavior in the Go/No-go task.

Ninety-six studies were meta-analyzed using a random effects model to examine the relationship between general impulsivity and alcohol use, as well as the relationships among separate impulsivity traits based in the UPPS model of impulsivity and specific alcohol use outcomes.

Results indicate that, in general, impulsivity and alcohol use are related (r = 0.28); however, this effect size varied significantly across studies (from −0.05 to 1.02). Drinking quantity was most strongly predicted by lack of perseverance (r = 0.32), whereas all traits equally predicted drinking frequency. Drinking problems were most highly related to negative (r = 0.35) and positive (r = 0.34) urgency, and alcohol dependence was most highly related to negative urgency (r = 0.38) and lack of planning (r = 0.37).

Effect sizes between impulsivity and alcohol use vary significantly by UPPS trait used in each study; thus, findings suggest and further reinforce the view in the literature that specific impulsivity-related constructs differentially relate to specific alcohol use outcomes.

A total of 53 Wistar rats were received at postnatal day (PD) 21 and were randomly assigned to EtOH vapor (14 hours on/10 hours off/day) or air exposure for 35 days from PD 23 to 58 (average blood ethanol concentration: 169 mg%). Animals were received in 2 groups that were subsequently sacrificed at 2 time points following withdrawal from EtOH vapor: (i) at 72 days of age, 2 weeks following withdrawal or (ii) at day 128, 10 weeks following withdrawal. In the second group, behavior in the light/dark box and prepulse inhibition (PPI) of the startle was also evaluated. Fifteen animals in each group were scanned, postmortem, for structural DTI.

There were no significant differences in body weight between EtOH and control animals. Volumetric data demonstrated that total brain, hippocampal, corpus callosum but not ventricular volume were significantly larger in the 128-day-sacrificed animals as compared to the 72 day animals. The hippocampus was smaller and the ventricles larger at 128 days as compared to 72 days, in the EtOH-exposed animals, leading to a significant group × time effect. EtOH-exposed animals sacrificed at 128 days also had diminished PPI, and more rears in the light box were significantly correlated with hippocampal size.

These studies demonstrate that DTI volumetric measures of hippocampus are significantly impacted by age and peri-adolescent EtOH exposure and withdrawal in Wistar rats.

A group of children with FASD (n = 27) between the ages of 8 and 16 and typically developing control children (n = 27) matched for age and sex, completed 3 saccadic eye movement tasks of increasing difficulty. Eye movement performance during the tasks was captured using an infrared eye tracker. Saccade metrics (e.g., velocity, amplitude, accuracy) were quantified and compared between the 2 groups for the 3 different tasks.

Children with FASD were more variable in saccade endpoint accuracy, which was reflected by statistically significant increases in the error of the initial saccade endpoint and the frequency of additional, corrective saccades required to achieve final fixation. This increased variability in accuracy was amplified when the cognitive demand of the tasks increased. Children with FASD also displayed a statistically significant increase in response inhibition errors.

These data suggest that children with FASD may have deficits in eye movement control and sensory-motor integration including cerebellar circuits, thereby impairing saccade accuracy.

This study therefore examined whether fathering by the biological father rather than another father figure, negative fathering, and gender role modeled by the father figure were significant predictors of involvement in MMARA, once drinking frequency and quantity and heavy episodic drinking were controlled for. A total of 121 university students aged 18 to 25 years (M = 20.63, SD = 1.77 years) voluntarily completed the online questionnaire.

The only significant predictors of perpetration of MMARA were a more abusive paternal relationship and drinking quantity (number of standard drinks usually consumed when drinking).

Negative father–son relationships may play a role in fostering young men's perpetration of MMARA in the barroom context.

Sixty individuals underwent a diffusion tensor imaging session and completed measures of alcohol consumption, loss of control over drinking, and aerobic exercise participation. Analyses examined the relationship of exercise, alcohol, and their interaction to fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF), external capsule (EC), superior and anterior corona radiata, and fornix. The relationship of aerobic exercise and alcohol consumption to self-reported loss of control over drinking were also examined.

A significant interaction was observed between alcohol consumption and aerobic exercise participation on FA in the SLF and EC. In the models examining loss of control over drinking, a significant interaction between aerobic exercise and alcohol consumption was observed, such that alcohol consumption was associated with loss of control more strongly for low exercisers than high exercisers.

These results indicate that the association between heavy alcohol consumption and WM damage in the EC and SLF and the association between alcohol consumption and loss of control over drinking are greater among individuals who do not exercise regularly. These results are consistent with the notion that exercise may protect WM integrity from alcohol-related damage.

Fourteen children (8 to 13 years) with FASD were recruited for oculomotor assessment and DTI. Eye movement control was evaluated using the pro- and antisaccade tasks, in which subjects look at (prosaccade) or away from (antisaccade) a peripheral target. Saccadic reaction time (SRT; time for subjects to move their eyes after the target appears) and direction errors (saccades made in the incorrect direction relative to the instruction) were measured and correlated to fractional anisotropy (FA) on a voxel-by-voxel basis across the whole brain white matter.

A significant positive correlation was observed between antisaccade SRT and FA in a large cluster containing anterior and posterior sections of the corpus callosum just to the right of the midline; prosaccade SRT and FA correlated positively in the genu of the corpus callosum and the right inferior longitudinal fasciculus (ILF), and correlated negatively in the left cerebellum.

The negative correlation for prosaccade SRT and cerebellum demonstrated that individuals with slower reaction times had lower FA values relative to their faster responding counterparts, a finding that implicates cerebellar dysfunction as a significant contributor to deficits in oculomotor control. The higher FA in the corpus callosum and ILF corresponding to longer reaction times for both pro- and antisaccade was opposite to what was expected, but nonetheless implies that altered brain structure in these regions underlies deficits in oculomotor control.

Using data from a randomized control trial delivered to 1,900 incoming college students, we examined differential treatment effects within 4 types of baseline student drinkers: (i) nondrinkers; (ii) weekend light drinkers (WLD); (iii) weekend heavy episodic drinkers; and (iv) heavy drinkers. The outcome variable was based on the transitions in drinking that occurred between the summer prior to college enrollment and the end of the first fall semester and distinguished between students who transitioned to 1 of the 2 risky drinking classes.

The results indicated that injunctive norms (but not descriptive norms or attitudes) moderated the differential effects of the PBI with strongest effects for students whose parents received the booster. Differential effects also depended on baseline drinking class and were most pronounced among WLDs who were deemed “high-risk” in terms of injunctive peer norms.

Parental influence can remain strong for young adults who are transitioning to college environments, even among students with relatively high peer influence to drink alcohol. Thus, the PBI represents an effective tool to prevent escalation of alcohol use during the first year of college, when risk is highest and patterns of alcohol use are established.

The subjects in this cross-sectional survey were 1,902 Japanese alcoholic men (≥40 years) who underwent ADH1B/ALDH2 genotyping.

Age-adjusted daily alcohol consumption did not differ according to the ADH1B/ALDH2 genotypes. The age-adjusted odds ratios (AORs; 95% confidence interval) for liver cirrhosis (LC; n = 359, 1.58 [1.19 to 2.09]), chronic calcific pancreatitis (CP; n = 80, 2.24 [1.20 to 4.20]), and diabetes mellitus (DM; n = 383, 1.51 [1.15 to 1.99]) were higher in the ADH1B*2 allele carriers than in the ADH1B*1/*1 carriers. The AORs for LC (1.43 [1.01 to 2.02]), CP (1.68 [0.80 to 3.53]), DM (1.63 [1.15 to 2.30]), and hypertension (HT; n = 495, 1.52 [1.11 to 2.07]) were higher in the ALDH2*1/*1 carriers than in the ALDH2*1/*2 carriers. The ADH1B*2-associated AOR for LC was 2.08 (1.46 to 2.94) among those aged 40 to 59 years, but 0.89 (0.56 to 1.43) among those aged 60 years or over, and the interaction between ADH1B genotype and age on the LC risk was significant (p = 0.009). When the group with non-LC and no/mild fibrosis was used as controls, the ADH1B*2-associated AORs increased according to the severity of their liver disease: 1.67 (1.32 to 2.11) for the group with non-LC and serum type IV collagen values ≥200 ng/ml, 1.81 (1.24 to 2.63) for the group of Child-Pugh class A LC, and 3.17 (1.98 to 5.07) for the group with Child-Pugh class B/C LC. Anti-hepatitis C virus (HCV) antibody was positive in 103 patients, and the groups with a high anti-HCV antibody titer and either the ADH1B*2/*2 genotype or the ALDH2*1/*1 genotype had the highest AORs (8.83 and 4.90, respectively). The population attributable fraction (PAF) due to the ADH1B*2 allele was 29% for LC, 47% for CP, and 27% for DM, and the PAF due to the ALDH2*1/*1 genotype was 26% for LC, 34% for DM, and 30% for HT.

The ADH1B*2 allele increased the AORs for LC, CP, and DM of the alcoholics, and the ALDH2*1/*1 genotype increased their AORs for LC, DM, and HT. HCV infection and genetic susceptibility had a synergistic effect on the AOR for LC.

This study examined negative mood states among 2 groups of 16- to 18-year-old high school students; youth with a history of recent heavy episodic drinking (HED; n = 39) and comparison youth with limited lifetime drinking experience (CON; n = 26). Affect was assessed at 3 time points during a 4- to 6-week period of monitored abstinence using the Hamilton Rating Scales for Anxiety and Depression; self-reports were obtained with the state portion of the State-Trait Anxiety Inventory, and experience sampling of current affect was assessed via daily text messages sent at randomly determined times in the morning, afternoon, and evening.

Youth with a recent history of HED reported more negative affect compared with nondrinking youth during early stages of abstinence (days since last HED at assessment 1: M = 6.46; SD = 5.06); however, differences in affect were not observed after 4 to 6 weeks of abstinence. Sex differences were evident, with HED girls reporting greater depression and anxiety than HED male peers. Although not significant, response patterns indicated that boys may experience faster resolution of negative emotional states than girls with sustained abstinence.

Findings suggest that high-dose drinking is associated with elevated negative affect for adolescents and that negative mood states may take longer to resolve for girls than for boys following heavy drinking episodes. Future research clarifying naturally occurring changes in affective response during early and sustained abstinence is necessary for improving programs designed to promote adolescent decision-making and to reduce risk for relapse.

In vivo MRS was used to measure the gray matter (GM) and white matter (WM) EtOH methyl ¹H MRS intensity in 18 adult male rhesus macaques at 4 time points throughout the course of a chronic drinking experiment. Time points were prior to EtOH drinking, following a 3-month EtOH induction procedure, and following 6, and 12 subsequent months of 22 h/d of “open access” to EtOH (4% w/v) and water.

The EtOH methyl ¹H MRS intensity, which we observed to be independent of age over the range examined, increased with chronic EtOH exposure in GM and WM. In GM, MRS intensity increased from naïve level following the EtOH induction period (90 g/kg cumulative EtOH intake). In WM, MRS intensity was not significantly different from the EtOH-naïve state until after 6 months of 22-hour free access (110 to 850 g/kg cumulative intake range). The WM MRS intensity in the EtOH-naïve state was positively correlated with future drinking, and the increase in WM MRS intensity was negatively correlated with the amount of EtOH consumed throughout the experiment.

Chronic exposure to EtOH is associated with brain changes that result in differential increases in EtOH MRS intensity in GM and WM. The EtOH-naïve WM MRS intensity pattern is consistent with its previously proposed relationship to innate tolerance to the intoxicating effects of EtOH. EtOH-dependent MRS intensity changes in GM required less EtOH exposure than was necessary to produce changes in WM. Within WM, an unexpected, potentially age dependent, enhanced sensitivity to EtOH in light drinkers relative to heavy drinkers was observed.

Naïve mice (N = 48/group) were genotyped using the Mouse Universal Genotyping Array, which provided 3,683 informative markers. Quantitative trait locus (QTL) analysis used a marker-by-marker strategy with the threshold for a significant logarithm of odds (LOD) set at 10.6. Gene expression in the ventral striatum was measured using the Illumina Mouse 8.2 array. Differential gene expression and the weighted gene coexpression network analysis (WGCNA) were implemented largely as described elsewhere.

Significant QTLs for elevated BECs after DID were detected on chromosomes 4, 14, and 16; the latter 2 were associated with gene-poor regions. None of the QTLs overlapped with known QTLs for EtOH preference drinking. Ninety-four transcripts were detected as being differentially expressed in both selected lines versus HS controls; there was no overlap with known preference genes. The WGCNA revealed 2 modules as showing significant effects of both selections on intramodular connectivity. A number of genes known to be associated with EtOH phenotypes (e.g., Gabrg1, Glra2, Grik1, Npy2r, and Nts) showed significant changes in connectivity.

We found marked and consistent effects of selection on coexpression patterns; DE changes were more modest and less concordant. The QTLs and differentially expressed genes detected here are distinct from the preference phenotype. This is consistent with behavioral data and suggests that the DID and preference phenotypes are markedly different genetically.

Ethanol (EtOH) or vehicle was administered to 4-month-old female Sprague–Dawley rats once daily at 1.2 g/kg body weight for 7 days. Following necropsy, bone formation and bone architecture were evaluated in tibial diaphysis (cortical bone) and proximal tibial metaphysis (cancellous bone) by histomorphometry. mRNA was measured for bone matrix proteins in distal femur metaphysis.

Administration of alcohol by gavage had no significant effect on body weight gain or bone measurements. In contrast, administration of the same dose of alcohol by ip injection resulted in reduced body weight, total suppression of periosteal bone formation in tibial diaphysis, decreased cancellous bone formation in proximal tibial metaphysis, and decreased mRNA levels for bone matrix proteins in distal femur.

Our findings raise concerns regarding the use of ip injection of EtOH in rodents as a method for modeling the skeletal effects of intermittent exposure to alcohol in humans. This concern is based on a failure of the ip route to replicate the oral route of alcohol administration.

Based on these findings, this study was sought to determine the efficacy of pioglitazone and naltrexone combination on alcohol intake and relapse behavior. Genetically selected alcohol-preferring Marchigian Sardinian (msP) rats were used for the study.

Pioglitazone (10 and 30 mg/kg) and naltrexone (0.25 and 1.0 mg/kg) each individually reduced alcohol drinking in msP rats. The combination of the 2 drugs resulted in a more potent alcohol drinking reduction than single agents. Confirming previous studies, pioglitazone (10 and 30 mg/kg) significantly reduced relapse induced by the pharmacological stressor yohimbine (1.25 mg/kg) but not by cues predictive of alcohol availability. Conversely, naltrexone reduced reinstatement of drug seeking elicited by alcohol cues but not by yohimbine.

The drug combination was effective in reducing both relapse behaviors. These findings open new vistas in the use pioglitazone in combination with naltrexone for the treatment of alcoholism.

In skin fibroblast cultures from well-characterized human AUD patients (n = 19) and controls (n = 13), we used a bioluminescent reporter gene (Per2::luc) to measure circadian rhythms in gene expression at high sampling density for 5 days. Cells were genotyped for the PER2 10870 variant. The rhythm parameters period and amplitude were then analyzed using a case–control design and by genetic and clinical characteristics of the AUD subjects.

There were no differences between AUD cases and controls in rhythm parameters. However, period was inversely correlated with illness severity (defined as the number of alcohol dependence criteria met). The PER2 variant 10870 was not associated with differences in rhythm parameters.

Our data suggest that differences in the cellular circadian clock are not pronounced in fibroblasts from AUD cases and controls. However, we found evidence that the circadian clock may be associated with an altered trajectory of AUD, possibly related to illness severity. Future work will be required to determine the mechanistic basis of this association.

In enriched neuronal cells from fetal rat hypothalami treated with EtOH or with conditioned medium from EtOH-treated microglia, we measured cellular apoptosis by the free nucleosome assay and the levels of cAMP, BDNF, O²⁻, reactive oxygen species (ROS), nitrite, glutathione (GSH), and catalase following treatment with EtOH or EtOH-treated microglial culture conditioned medium. Additionally, we tested the effectiveness of dbcAMP and BDNF in preventing EtOH or EtOH-treated microglial conditioned medium on cellular apoptosis and oxidative stress in enriched hypothalamic neuronal cell in primary cultures.

Neuronal cell cultures following treatment with EtOH or EtOH-activated microglial conditioned medium showed decreased production levels of cAMP and BDNF. EtOH also increased apoptotic death as well as oxidative status, as demonstrated by higher cellular levels of oxidants but lower levels of antioxidants, in neuronal cells. These effects of EtOH on oxidative stress and cell death were enhanced by the presence of microglia. Treatment with BDNF or dbcAMP decreased EtOH or EtOH-activated microglial conditioned medium-induced changes in the levels of intracellular free radicals, ROS and O²⁻, nitrite, GSH, and catalase.

These data support the possibility that EtOH by acting directly and via increasing the production of microglial-derived factors reduces cellular levels of cAMP and BDNF to increase cellular oxidative status and apoptosis in hypothalamic neuronal cells in primary cultures.

PB samples from 25 male patients with AH were studied; in parallel, 15 male chronic alcoholic patients without liver disease (AWLD) and 17 male healthy donors were also studied, as controls. The distribution of CD4⁺CD25^hiCD127^−/lo Tregs and their maturation subsets (naïve, central memory, and peripheral memory Tregs) was analyzed by flow cytometry. Spontaneous and in vitro-stimulated production of inflammatory cytokines by PB monocytes and DCs was analyzed by flow cytometry at the cytoplasmic level.

Patients with AH showed decreased (p < 0.05) numbers of PB CD4⁺CD25^hiCD127^−/lo Tregs at the expense of all maturation-associated subsets, while AWLD and healthy subjects showed a similar (p > 0.05) distribution of PB CD4⁺CD25^hiCD127^−/lo Tregs. Interestingly, significantly increased amounts of spontaneously produced inflammatory cytokines were found among circulating monocyte-derived DCs and monocytes from AH (and AWLD) patients in comparison with healthy donors. Conversely, the ability of these cell subsets to produce cytokines after in vitro stimulation was lower (p < 0.05) in AH versus the 2 control groups.

PB CD4⁺CD25^hiCD127^−/lo Tregs are significantly decreased in patients with AH when compared to both healthy and AWLD; this may contribute to explain the more pronounced activation of the innate immune response observed in AH, as reflected by an increased secretion of inflammatory cytokines by PB DCs and monocytes, and could facilitate the development of liver disease.

Male young adult (postnatal day 70 to 72) and aged (~18 months) Sprague-Dawley rats were assessed on 2 motor tasks (the accelerating rotarod [RR] and the aerial righting reflex [ARR]) and a single cognitive performance task (the Morris water maze [MWM]). Following acute EtOH exposure via intraperitoneal injection, animals' performance was reassessed.

Aged rats showed a dramatic increase in EtOH-induced ataxia on the RR and the ARR relative to young adult animals. Similarly, results from the MWM revealed that aged animals had slightly greater EtOH-induced impairments compared with young adult animals. Importantly, the increased impairments produced by EtOH were not due to differential blood EtOH levels.

We demonstrate for the first time that aged rats show greater EtOH-induced deficits compared with young adults in tasks of motor and cognitive performance. The possible role of protein kinase C as a mechanism for increased sensitivity to the motor-impairing effects of EtOH is discussed. Given the high prevalence of alcohol use among the elderly, increased vulnerability to alcohol-induced deficits may have a profound effect on injury in this population.

Two-month-old Wistar-derived UChB alcohol drinker rats were offered free access to water and 10 and 20% EtOH for 67 days. Thereafter, the animals were deprived of EtOH for 15 days and were subsequently offered access to the EtOH solutions. At the start of the deprivation period, animals were microinjected a single dose of an anticatalase (or control) vector into the VTA. EtOH intake was measured on the first hour of EtOH re-exposure as well as on a 24-hour basis for 7 days.

A marked ADE was observed when EtOH intake was measured on the first hour or 24 hours following EtOH re-exposure, compared to the corresponding controls. The administration of the anticatalase vector reduced ADE by 60 to 80% (p < 0.001) on the first hour and by 63 to 80% (p < 0.001) on the initial 24 hours of EtOH re-exposure (first and second ADE, respectively) without changing the total fluid intake, indicating a specific effect on EtOH drinking.

Ethanol intake associated with ADE—a binge-like drinking behavior—is markedly inhibited by the administration of an anticatalase vector into the VTA, which blocks the conversion of EtOH into acetaldehyde, strongly suggesting that the marked increased EtOH intake that follows an alcohol deprivation period is mediated by acetaldehyde and its reinforcing metabolite.

During 4 randomized double-blind sessions, participants assessed the effects of nicotine-containing tobacco or denicotinized tobacco following the administration of a moderately intoxicating dose of alcohol (mean blood alcohol concentration = 0.076 g/dl) or a placebo beverage. They could then self-administer additional puffs of the same type of cigarette sampled over a 60-minute period using a progressive ratio task.

In NNS, alcohol significantly increased the self-administration of both nicotine-containing and denicotinized cigarettes, and no differences in self-administration were observed between the 2 types of tobacco within either beverage condition. In contrast, in DDS, alcohol was associated with decreased denicotinized tobacco self-administration relative to the placebo beverage condition as well as with increased self-administration of nicotine-containing tobacco relative to denicotinized tobacco. DDS also exhibited relatively elevated craving following the administration of a nicotine-containing cigarette in the alcohol beverage condition.

Findings suggest that nicotine may be critical to the drinking–smoking relationship in DDS, but that nonnicotine smoking factors may be more important in NNS.

Primary rat cardiac fibroblasts were cultured in the presence of ethanol (EtOH) and assayed for fibroblast activation by collagen gel contraction, alpha-smooth muscle actin (α-SMA) expression, migration, proliferation, apoptosis, collagen I and III, and TGF-β expression. The TGF-β receptor type 1 inhibitor compound SB 431542 and a soluble recombinant TGF-βII receptor (RbII) were used to assess the role of TGF-β in the response of cardiac fibroblasts to EtOH.

Treatment for cardiac fibroblasts with EtOH at concentrations of 100 mg/dl or higher resulted in fibroblast activation and fibrogenic activity after 24 hours including an increase in contraction, α-SMA expression, migration, and expression of collagen I and TGF-β. No changes in fibroblast proliferation or apoptosis were observed. Inhibition of TGF-β by SB 431542 and RbII attenuated the EtOH-induced fibroblast activation.

EtOH treatment directly promotes cardiac fibroblast activation by stimulating TGF-β release from fibroblasts. Inhibiting the action of TGF-β decreases the fibrogenic effect induced by EtOH treatment. The results of this study support TGF-β to be an important component in cardiac fibrosis induced by exposure to EtOH.

A random sample of incoming freshmen (n = 387, 59% female) completed measures of AMED use, AMED-specific expectancies, attitudes, and normative beliefs, and drinking quantity and alcohol-related consequences. Data were collected at 2 occasions: spring semester of freshmen year and fall semester of sophomore year.

Latent profile analysis identified 4 subgroups of individuals: occasional AMED, anti-AMED, pro-AMED, and strong peer influence. Individuals in the pro-AMED group reported the most AMED use, drinking, and consequences. There was a unique association between profile membership and AMED use, even after controlling for drinking.

Findings highlighted the importance of AMED-specific expectancies, attitudes, and norms. The unique association between AMED risk profiles and AMED use suggests AMED use is a distinct behavior that could be targeted by AMED-specific messages included in existing brief interventions for alcohol use.

Adult male Sprague-Dawley rats were subjected to a 4-day binge-like EtOH administration regimen (3 to 5 g/kg/i.g. every 8 hours designed to produce peak blood EtOH levels (BELs) of <300 mg/dl). Subgroups of animals received s.c. injection of the GR antagonist mifepristone (20 or 40 mg/kg in peanut oil at 0800 hours on each of the 4 days prior to withdrawal). BELs were assessed at 0900 and 1500 hours on Days 2 (D2) and 4 (D4) of the regimen. BEL, blood corticosterone levels (BCLs), and EtOH withdrawal–associated behavioral abnormalities were assessed 10 to 12 hours after the final EtOH administration.

Daily mean EtOH doses for D1 to D4 of the regimen were 14.4, 9.9, 7.1, and 8.6 g/kg, respectively. The EtOH gavage regimen produced mean BELs of 255 mg/dl at 0900 on D2 and 156.2 mg/dl at 0900 on D4 of the regimen. Withdrawal from the EtOH exposure regimen, beginning 10 hours after the last EtOH administration, produced significant elevations in BCL and behavioral abnormalities including tremors, stereotypy, and “wet dog shakes.” Mifepristone administration did not alter food intake or weight during the 4-day regimen, nor were there drug-dependent differences in BEL or BCL on withdrawal day. Although mifepristone produced no significant changes in behavior of EtOH-naïve animals, pretreatment with mifepristone (40 mg/kg) significantly reduced the severity of EtOH withdrawal.

Findings suggest that activation of GRs promotes neuroadaptation to binge-like EtOH exposure, contributing to the development of EtOH dependence. Further, GRs may represent therapeutic targets to be exploited in reducing the severity of EtOH withdrawal.

Whole-cell voltage-clamp recordings were performed at 32 to 34°C in both HEK cell lines and DRG neurons. The recordings were taken after a 10-minute application of EtOH or protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate [PMA]).

We recorded T-type Ca²⁺ currents (T-currents) from 3 channel isoforms (Ca_V3.1, Ca_V3.2, and Ca_V3.3) before and during administration of EtOH. We found that only 1 isoform, Ca_V3.2, was significantly affected by EtOH. EtOH reduced current density as well as producing a hyperpolarizing shift in steady-state inactivation of both Ca_V3.2 currents from HEK 293 cell lines and in native T-currents from DRG neurons that are known to be enriched in Ca_V3.2. A myristoylated PKC peptide inhibitor (MPI) blocked the major EtOH effects, in both the cell lines and the DRG neurons. However, PMA effects were more complex. Lower concentration PMA (100 nM) replicated the major effects of EtOH, while higher concentration PMA (1 μM) did not, suggesting that the EtOH effects operate through activation of PKC and were mimicked by lower concentration of PMA.

EtOH primarily affects the Ca_V3.2 isoform of T-type Ca²⁺ channels acting through PKC, highlighting a novel target and mechanism for EtOH effects on excitable membranes.

Mice were injected with saline or EtOH (0.5 to 2.5 g/kg) once a day for 10 days. Mice received NaB (200 to 600 mg/kg) 30 minutes before each injection (prevention protocol) or once daily between days 11 and 16 (reversal protocol). At day 17, brains were removed 30 minutes after a saline or EtOH challenge to assess gene and proteins levels.

Only the intermediate EtOH doses (1.0 and 2.0 g/kg) were effective in inducing EIBS, and both doses were associated with specific gene regulations in the striatum. The induction of sensitization by 1.0 g/kg (but not 2.0 g/kg) EtOH was dose-dependently prevented or reversed by NaB. Among the 168 studied genes, EIBS blockade was associated with specific gene regulations (bcl-2, bdnf, hdac4, pak1, penk, tacr1, vip…) and changes in brain-derived neurotrophic factor in both striatum and prefrontal cortex.

These results indicate that EIBS is associated with specific gene regulations in the striatum depending on the EtOH dose and that NaB can be useful in blocking some long-lasting neuro-adaptations to repeated EtOH administrations.

Using a placebo-controlled, single-blind, cross-over design, participants (n = 28) attended 4 sessions in which they were administered, in counterbalanced order: 0.5 g/kg alcohol, 3.57 ml/kg ED, AmED, and a placebo beverage. Participants completed the Biphasic Alcohol Effects Scale and a Subjective Effects Scale at baseline and 30 and 125 minutes postbeverage administration; risk-taking was measured using the Balloon Analogue Risk Task (BART).

Participants reported greater subjective intoxication, impairment, and sedation after active relative to placebo alcohol consumption, with no interactive AmED effects. However, a significant moderate magnitude increase in stimulation ratings was observed in the AmED relative to alcohol, ED, and placebo conditions. There was no independent effect of alcohol, or interactive effect with ED, on the BART. A significant, yet small magnitude, increase in risk-taking was evident in active relative to placebo ED conditions.

The interactive effect of AmED appears restricted to perceived stimulation, with alcohol-induced increases in subjective intoxication occurring regardless of presence or absence of ED. Engagement in risk-taking behavior was only increased by ED consumption; however, this effect was only of small magnitude; at these doses, alcohol consumption, with or without EDs, did not affect risk-taking. Further research assessing the dose-dependent effects of AmED on objectively measured risk-taking behavior could clarify whether the ED effect increases with higher doses and whether an interactive effect is observed with higher alcohol doses.

Primary neurosphere cultures were maintained under conditions promoting the stem cell state and treated with EtOH for 5 days. Control and EtOH-treated cellular extracts were examined using a combination of quantitative RT-PCR and chromatin immunoprecipitation techniques.

We find that the regulatory regions of genes controlling both neural precursor cell identity and processes of differentiation exhibited significant declines in the enrichment of the chromatin marks examined. Despite these widespread changes in chromatin structure, only a small subset of genes including Dlx2, Fabp7, Nestin, Olig2, and Pax6 displayed EtOH-induced alterations in transcription. Unexpectedly, the majority of chromatin-modifying enzymes examined including members of the Polycomb Repressive Complex displayed minimal changes in expression and localization. Only transcripts encoding Dnmt1, Uhrf1, Ehmt1, Ash2 l, Wdr5, and Kdm1b exhibited significant differences.

Our results indicate that primary neurospheres maintained as stem cells in vitro are susceptible to alcohol-induced perturbation of the histone code and errors in the epigenetic program. These observations indicate that alterations to chromatin structure may represent a crucial component of alcohol teratogenesis and progress toward a better understanding of the developmental origins of fetal alcohol spectrum disorders.

Development of the seminiferous tubules and the onset of spermatogenesis were examined utilizing a rat model of fetal alcohol spectrum disorder (FASD). Male offspring from ad libitum-fed control (C), pair-fed (PF), and EtOH-fed (prenatal alcohol exposure [PAE]) dams were terminated on postnatal (PN) days 5, 15, 18, 20, 25, 35, 45, and 55, to investigate morphological changes through morphometric analysis of the testes from early neonatal life through young adulthood.

PAE males had lower relative (adjusted for body weight) testis weights compared with PF and/or C males from PN15 through puberty (PN45). In addition, fewer gonocytes (primordial germ cells) were located on the basal lamina on PN5, while more of those touching the basal lamina were dividing in PAE compared with PF and C males, suggesting delayed cell division and migration processes. As well, the percentage of tubules with open lumena was lower in PAE compared with PF and C males on PN18 and 20, and PAE males had fewer primary spermatocytes per tubule on PN18 and round spermatids per tubule on PN25 compared with C males. Finally, the percentage of tubules at stages VII and VIII, when mature spermatids move to the apex of the epithelium and are released, was lower in PAE compared with PF and/or C males in young adulthood (PN55).

Maternal EtOH consumption appears to delay both reproductive development and the onset of spermatogenesis in male offspring, with effects persisting at least until young adulthood.

This study investigated abstinent alcohol-dependent participants (AADs; n = 31), who had a drinking history of levels about 97 drinks per week (abstinence range: 2 weeks to 24 months), actively drinking problem drinkers (PRDs; n = 23), who reported drinking levels about 47 drinks per week and who were abstinent for at least 24 hours, and healthy control (HC) participants (n = 20). It was investigated how participants responded to a psychosocial stress task. All of them were exposed to a modified Trier Social Stress Test. Salivary cortisol, heart rate, skin conductance levels, and negative affect were assessed as stress indicators.

AADs showed stress reactions comparable to HC participants, whereas active PRDs showed increased heart rate and cortisol stress responses. In the AAD group, duration of abstinence was positively related to cortisol stress responses.

Active PRDs showed increased responses to psychosocial stress. Results indicate that duration of abstinence is a key factor when analyzing and interpreting stress responses in alcohol abuse and dependence.

To determine whether rare variants in the CHRNA5-A3-B4 gene cluster contribute to the LR to alcohol, the coding regions of these 3 genes were sequenced in 538 subjects from the San Diego Sibling Pair study.

The analyses identified 16 rare missense variants, 9 of which were predicted to be damaging using in silico analysis tools. Carriers of these variants were compared to noncarriers using a family-based design for each gene and for the gene cluster as a whole. In these analyses, a CHRNA5 carrier status was significantly associated with the phenotype related to the feeling of intoxication experienced during the alcohol challenge (p = 0.039).

These results indicate that rare genetic variation in the CHRNA5-A3-B4 gene cluster contributes modestly to the LR to alcohol in the San Diego Sibling Pair study and may protect against AUDs. However, replication studies are needed to confirm our findings.

The male subjects (98% Caucasian) for this study were 129 probands from the San Diego Prospective Study who were first evaluated at age 20 as drinking but not alcohol-dependent young men, most of whom were college graduates by follow-up. The individuals evaluated here met criteria for an AUD at their first follow-up at ages 28 to 33 and were followed every 5 years for the next 2 decades. Discrete-time survival analysis was used to examine rates of initial and sustained AUD remission and to evaluate the relationships of premorbid characteristics and other risk factors to these outcomes.

Sixty percent of the sample met criteria for an initial AUD remission of 5 or more years, including 45% with sustained remission (i.e., no subsequent AUD diagnosis). Higher education, lower drinking frequency, and having a diagnosis of alcohol abuse (rather than dependence) were associated with higher rates of initial AUD remission. A lower LR to alcohol at age 20, as well as lower drinking frequency, having received formal alcohol treatment, and older age at the first follow-up all predicted a greater likelihood of sustained AUD remission.

This study identified key factors associated with initial and sustained AUD remission in subjects diagnosed with AUD in young adulthood. Characteristics associated with better outcomes early in the life span, such as lower drinking frequency and early treatment, appear to have a lasting impact on remission from AUD across adulthood.

Participants were drawn from the Veterans Aging Cohort Study that included HIV-positive and matched non-HIV participants. As in our earlier studies, the lifetime drinking history was used to assess drinking phases, and latent growth mixture models were used for analyses.

Similar to previous findings, both the HIV+ and non-HIV groups exhibited 4 patterns of drinking (SC, SNC, LO, and YA). SC drinkers had younger ages of onset for drinking and longer duration of smoking. SC drinkers also had the highest rates of cocaine use. Within the HIV+ subsample, SC and LO drinkers increased their drinking after their HIV diagnosis.

This study is the first to examine lifetime drinking patterns among those treated for HIV and provides an excellent starting point for examining finer-grained relationships involving drinking, onset of HIV, and treatment outcomes. Absent from the current study and of particular importance to future work in this area is the need for precise information regarding the temporal relationship between date of HIV diagnosis, onset of treatment, and changes in drinking behavior over the life course.

Since 2007, alcohol intoxication among adolescents has been one of the leading topics of the Dutch Pediatric Surveillance System. In the current study, we have analyzed which demographic characteristics, general alcohol use behaviors, and clinical intoxication data were related to the blood alcohol concentration (BAC) levels at hospital admittance. We included all adolescents aged <18 years, admitted with BAC >0.0 g/l, and reduced consciousness during the years 2007, 2008, 2009, and 2010.

A total of 2,023 adolescents with alcohol intoxication were reported, and 1,618 questionnaires were returned, of which 1,350 met our inclusion criteria.

In univariate analysis, age, gender, educational level, place of alcohol purchase, place of alcohol consumption, age of first drink, and regular alcohol use during the weekend correlated with higher BAC. After multivariate analysis, older adolescents, boys, and higher educational level significantly attributed to higher BAC at admittance.

In alcohol-intoxicated adolescents with reduced consciousness, gender, age, and also educational level correlate with BAC at admittance. Explanatory factors could be found in sensitivity to alcohol, but also in socioeconomic factors, which influence availability. Intervention strategies could be targeted more specific now for the subgroups found in this study to decrease the growing burden of adolescent alcohol intoxication, both on the societal level and on the clinical level.

Driver records and interlock program records covering 120,000 DUI offenders were followed over 10 years. The flow through the sanction system—conviction, reinstatement, interlock program, and postinterlock period—is described. Logistical regression was used to identify the characteristics of offenders who installed interlocks, and survival analysis was used to evaluate the recidivism of offenders in the various stages in the ARIP.

At any given time, approximately one-third of the convicted offenders were serving their license-revocation periods. Half of the offenders who completed their revocation periods remain unqualified for reinstatement because they do not fulfill other requirements. ARIP offenders who do qualify for reinstatement and install interlocks have lower recidivism rates while the devices are on their vehicles.

After 10 years, Florida's ARIP is a mature system that succeeds in forcing all offenders in the program who qualify for reinstatement to install an interlock for at least 6 months. However, half of all offenders who complete their mandatory revocation period are either unable to or choose not to qualify for reinstatement.

These data are from a longitudinal study of PAE. Mothers were recruited from a prenatal clinic and interviewed during their fourth prenatal month, seventh month, and delivery. In the postpartum, mothers and offspring were seen at 8 and 18 months, and 3, 6, 10, 14, 16, and 22 years.

At 22 years, PAE significantly predicted behavior as measured with the adult self-report. These findings were significant controlling for covariates. Exposure at each trimester predicted increased behavior problems on the Total Score, Internalizing, Externalizing, Attention, and Critical Items scales. Use across pregnancy predicted a higher rate of behavior problems compared to no use and use in the first trimester only.

The effects were dose-response and significant at each trimester of pregnancy. However, duration across pregnancy was a better predictor than drinking during the first trimester only. Binge drinking was not a better predictor of outcome compared to average daily volume (ADV), and within categories of ADV, binge drinking did not predict more problems than nonbinge drinking. Thus, there is no safe level or safe time during pregnancy for women to drink. These data demonstrate that the effects of PAE, even at low to moderate levels, extend into young adulthood and are most likely permanent.

A study was conducted in which pseudo-intoxicated actors tried to order alcoholic drinks in 58 bars. A 2 × 2 design was used, based on (i) the number of actors involved (1 vs. 2) and (ii) the level of intoxication (moderately vs. very drunk). In contrast to earlier studies, research accomplices checked afterward whether the bartenders noticed that the actors appeared intoxicated.

In 86% of the cases, the actors were able to buy alcohol, without comments or questions. In 10%, the actors were refused entrance by a bouncer. Only in 4%, the bartender refused to serve. In 81% of the cases, the bartenders remembered the actors: In 93% of those cases, they noticed that the actor appeared intoxicated. Only the “very drunk” script involving 2 actors led to refusals.

The results show that compliance with the regulations regarding overserving to intoxicated guests is problematic in the Netherlands. Misinterpretations of the situation could be ruled out: Most bartenders noticed that the actors appeared intoxicated but served nonetheless.

Neurocognitive functions previously shown to be adversely affected by both alcohol use disorders and chronic cigarette smoking were evaluated. We assessed 35 smoking ALC (sALC) and 34 nonsmoking ALC (nsALC) at approximately 1 and 5 weeks of monitored abstinence.

Although neither group was clinically impaired, both cross-sectional and longitudinal deficiencies were observed in sALC versus nsALC in processing speed, working memory, and auditory-verbal learning and memory. Lifetime alcohol consumption, medical, and psychiatric comorbidities did not predict neurocognitive performance or improvement across assessments. Within sALC, greater drinking and smoking severities were synergistically (more than additively) related to less improvement on visuospatial learning and memory. Former smoking status in the nsALC-mediated group differences in auditory-verbal delayed recall.

Chronic cigarette smoking appears to negatively impact neurocognition during early abstinence from alcohol. Although the cognitive deficiencies observed in this cohort were not in a clinical range of impairment, they should be considered to enhance treatment efficacy. Our findings lend support to integrating smoking cessation as well as the individual assessment of cognition into early ALC treatment. Additionally, there is a need to elucidate the effects of current and former smoking status in future reports of neurocognition.

We made whole-cell recordings of GABA_A receptor-mediated tonic inhibitory currents from dentate gyrus granule cells (DGGCs) in hippocampal slices from adult rats that had been treated with chronic intermittent ethanol (CIE) or saline during adolescence, young adulthood, or adulthood.

CIE reduced baseline tonic current amplitude in DGGCs from animals pretreated with EtOH during adolescence, but not in GCs from those pretreated with EtOH during young adulthood or adulthood. Similarly, the enhancement of tonic currents by acute EtOH exposure ex vivo was increased in GCs from animals pretreated with EtOH during adolescence, but not in those from animals pretreated during either of the other 2 developmental periods.

These findings underscore our recent report that CIE during adolescence results in enduring alterations in tonic current and its acute EtOH sensitivity and establish that adolescence is a developmental period during which the hippocampal formation is distinctively vulnerable to long-term alteration by chronic EtOH exposure.

Doses of varenicline (0.56 to 5.6 mg/kg, i.p.) or vehicle were administered 30 minutes before sessions. Effects of varenicline on responding across the session and during each tenth of the session were compared to responding following vehicle treatment.

Lower doses (0.56 to 1.0 mg/kg) of varenicline increased responding for EtOH without affecting responding for food. Higher doses disrupted responding for EtOH and food similarly.

Previous reports of varenicline selectivity on EtOH-maintained responding do not generalize to other experimental conditions such as a concurrent schedule. The increase in responding for EtOH following lower doses might be due to enhanced EtOH reinforcement, decreased food reinforcement, rate dependency, or greater perseverance on the initial, EtOH response.

We performed a prospective follow-up study of 678 women and their children sampled from the Danish National Birth Cohort based on maternal alcohol consumption during pregnancy. At 5 years of age, the children were tested with the Movement Assessment Battery for Children. Parental education, maternal IQ, prenatal maternal smoking, the child's age at testing, sex of child, and tester were considered core confounders, while the full model also controlled for prenatal maternal average alcohol intake, maternal age and prepregnancy body mass index, parity, home environment, postnatal parental smoking, health status, participation in organized sport, and indicators for hearing and vision impairment.

There were no systematic or significant differences in motor function between children of mothers reporting isolated episodes of binge drinking and children of mothers with no binge episodes. No association was observed with respect to the number of binge episodes (maximum of 12) and timing of binge drinking.

In this study, we found no systematic association between isolated episodes of binge drinking during early pregnancy and child motor function at age 5.

We evaluated associations between ADH1B/ALDH2 genotypes and the body weight and body mass index (BMI) of 1,301 Japanese alcoholic men at the time of their first visit to an addiction center.

Median (25th to 75th) caloric intake in the form of alcoholic beverages was 864 (588 to 1,176) kcal/d. Age-adjusted caloric intake did not differ according to ADH1B/ALDH2 genotypes. The body weight and BMI values showed that the ADH1B*2/*2 and *1/*2 carriers (n = 939) were significantly leaner than the ADH1B*1/*1 carriers (n = 362) irrespective of age, drinking, smoking, and dietary habits. The age-adjusted body weight values of the ADH1B*2/*2, ADH1B*1/*2, and ADH1B*1/*1 carriers were 58.4 ± 0.4, 58.7 ± 0.5, and 63.6 ± 0.5 kg, respectively (ADH1B*2 vs. ADH1B*1/*1 carriers, p < 0.0001), and the corresponding BMI values were 21.0 ± 0.1, 21.0 ± 0.1, and 22.9 ± 0.2 kg/m², respectively (ADH1B*2 vs. ADH1B*1/*1 carriers, p < 0.0001). No effects of inactive ALDH2 on body weight or BMI were observed. A multivariate analysis showed that BMI decreased by 0.35 per 10-year increase in age, by 1.73 in the presence of the ADH1B*2 allele, by 1.55 when the preferred beverage was whiskey, and by 0.19 per +10 cigarettes/d and that it increased by 0.10 per +22 g ethanol (EtOH)/d and by 0.41 per increase in category of frequency of milk intake (every day, occasionally, rarely, and never). The increase in BMI as alcohol consumption increased was significantly smaller in the ADH1B*2 group than in the ADH1B*1/*1 group (p = 0.002).

ADH1B genotype was a strong determinant of body weight in the alcoholics. The more rapid EtOH elimination associated with the ADH1B*2 allele may result in less efficient utilization of EtOH as an energy source in alcoholics.

HIV-1Tg and control F344 rats were administered water, 8% EtOH, or 52% EtOH by gavage (i.g.) for 3 days (2.0 g/kg/d). Two hours after final treatment, blood, liver, and spleen were collected from each animal. Serum blood EtOH concentration (BEC) was measured, and gene expression in the liver and spleen was determined using a specifically designed PCR array.

The BEC was significantly higher in the 52% EtOH-treated HIV-1Tg rats compared with the 8% EtOH group; however, the BEC was higher in the 8% EtOH-treated control rats compared with the 52% EtOH group. There was no change in expression of the EtOH metabolism-related genes, Adh1, Adh4, and Cyp2e1, in either the 8 or 52% EtOH-treated HIV-1Tg rats, whereas expression of those genes was significantly higher in the liver of the 52% EtOH control rats, but not in the 8% EtOH group. In the HIV-1Tg rats, expression of the GABA_A, metabotropic glutamate, and dopamine neurotransmitter receptor genes was significantly increased in the spleen of the 52% EtOH group, but not in the 8% EtOH group, whereas no change was observed in those genes in either of the control groups.

Our data indicate that, in the presence of HIV-1 infection, EtOH concentration-dependent binge drinking can have significantly different molecular effects.

Pregnant rat dams were fed with alcohol-containing liquid diet or control diet during gestational days 7 and 21 with or without choline, and their male offspring rats were used during the adult period. Using double-immunohistochemistry, real-time reverse transcription polymerase chain reaction (RT-PCR) and methylation-specific RT-PCR, we determined protein and mRNA levels of histone-modifying and DNA-methylating enzymes and the changes in POMC gene methylation and expression in the hypothalamus of adult male offspring rats. Additionally, we measured the basal- and lipopolysaccharide (LPS)-induced corticosterone levels in plasma by enzyme-linked immunosorbent assay.

Prenatal EtOH treatment suppressed hypothalamic levels of protein and mRNA of histone activation marks (H3K4me3, Set7/9, acetylated H3K9, phosphorylated H3S10), and increased the repressive marks (H3K9me2, G9a, Setdb1), DNA-methylating enzyme (Dnmt1), and the methyl-CpG-binding protein (MeCP2). The treatment also elevated the level of POMC gene methylation, while it reduced levels of POMC mRNA and β-EP and elevated corticosterone response to LPS. Gestational choline normalized the EtOH-altered protein and the mRNA levels of H3K4me3, Set7/9, H3K9me2, G9a, Setdb1, Dnmt1, and MeCP2. It also normalizes the changes in POMC gene methylation and gene expression, β-EP production, and the corticosterone response to LPS.

These data suggest that prenatal EtOH modulates histone and DNA methylation in POMC neurons that may be resulting in hypermethylation of POMC gene and reduction in POMC gene expression. Gestational choline supplementation prevents the adverse effects of EtOH on these neurons.

We obtained a national sample of 1,032 underage youth, aged 13 to 20, using a pre-recruited Internet panel maintained by Knowledge Networks. Youth aged 18 to 20 were recruited directly from the panel via email invitation. Teens aged 13 to 17 were identified by asking adult panelists to identify a member of their household. The survey assessed the past 30-day consumption of 898 brands of alcohol among 16 alcoholic beverage types, including the frequency and amount of each brand consumed in the past 30 days. Market share for a given brand was calculated by dividing the total number of drinks for that brand in the past 30 days across the entire sample by the total number of drinks for all identified brands.

The alcohol brands with highest prevalence of past 30-day consumption were Bud Light (27.9%, 95% confidence interval [CI] 23.3 to 32.4%), Smirnoff malt beverages (17.0%, 95% CI 12.9 to 21.1%), and Budweiser (14.6%, 95% CI 11.0 to 18.3%). Brand market share was concentrated in a relatively small number of brands, with the top 25 brands accounting for nearly half of all market shares.

Underage youth alcohol consumption, although spread out over several alcoholic beverage types, is concentrated among a relatively small number of alcohol brands. This finding has important implications for alcohol research, practice, and policy.

Rats were trained to self-administer 10% alcohol or 1.5% sucrose in a lever-press task and then underwent a within-subject assessment of NTX (0.1 to 1 mg/kg) effects on operant behavior. A fixed-ratio (FR5) reinforcement schedule was used to model goal-directed behavior, and a variable-interval (VI30) schedule was used to model habitual behavior.

As predicted, NTX reduced fluid deliveries earned by the FR5-alcohol group significantly more than all other groups. However, NTX reduced lever presses during self-administration sessions in VI30-trained rats without reducing earned deliveries, due to the low contingency between rate of pressing and fluid deliveries under that schedule. Interestingly, when fluid delivery was withheld (extinction), NTX reduced reward-seeking in all rats. Finally, NTX blocked reinstatement of reward-seeking upon presentation of 0.2 ml alcohol or sucrose and associated cues in the FR5-trained but not VI30-trained rats.

NTX reduced goal-directed alcohol drinking compared with other operant conditions. In addition, NTX blocked reinstatement of reward-seeking in rats trained on the goal-directed FR5 reinforcement schedule but not in rats trained on the habit-like VI30 reinforcement schedule. However, NTX also exerted nonspecific effects on reward-seeking that were revealed under low-effort contingency conditions or absence of reward. Together, these data support the hypothesis that NTX is less effective in conditioning models that are more habit-associated.

We evaluated the selectivity of CRF1 involvement in binge-like EtOH intake by interrupting CRF1 function via pharmacological and genetic methods in a slightly modified 2-bottle choice DID model that allowed calculation of an EtOH preference ratio. In addition to determining EtOH intake and preference, we also measured consumption of food and H₂O during the DID period, both in the presence and absence of EtOH and sweet tastant solutions.

Treatment with either of the CRF1-selective antagonists CP-376,395 (CP; 10 to 20 mg/kg, i.p.) or NBI-27914 (10 to 30 mg/kg, i.p.) decreased intake of 15% EtOH in male C57BL/6J mice, but did so in the absence of a concomitant decrease in EtOH preference. These findings were replicated genetically in a CRF1 knockout (KO) mouse model (also on a C57BL/6J background). In contrast to effects on EtOH intake, pharmacological blockade of CRF1 with CP increased intake of 10% sucrose, consistent with previous findings in CRF1 KO mice. Finally, pharmacological and genetic disruption of CRF1 activity significantly reduced feeding and/or total caloric intake in all experiments, confirming the existence of nonspecific effects.

Our findings indicate that blockade of CRF1 receptors does not exert specific effects on EtOH intake in the DID paradigm, and that slight modifications to this procedure, as well as additional consummatory control experiments, may be useful when evaluating the selectivity of pharmacological and genetic manipulations on binge-like EtOH intake.

We studied the temporal relationship of steatosis and glucose homeostasis in mice fed a Lieber–DeCarli liquid control or ethanol (EtOH) diet for 2, 4, or 8 weeks. We studied the effects of alcohol consumption on energy balance, body composition, and hepatic lipids. Glucose tolerance test was performed, and insulin sensitivity was evaluated with hyperinsulinemic-euglycemic clamp.

EtOH-fed mice developed hepatic steatosis over time as compared with control-fed mice despite similar energy intake and expenditure, and gain in body weight and fat. EtOH-fed mice developed glucose intolerance as early as 2 weeks, while insulin resistance developed at 4 weeks. A hyperinsulinemic clamp study at 8 weeks revealed both hepatic and peripheral insulin resistance in EtOH-fed mice. Insulin resistance was associated with hepatic steatosis, increased ceramide levels, and Perilipin 2 expression.

Chronic EtOH consumption leads to the development of hepatic steatosis, impaired glucose tolerance, and insulin resistance. These changes are independent of energy intake or expenditure, weight, whole body fat content, and inflammation. A better understanding of the processes linking EtOH-induced steatosis and abnormal glucose homeostasis may lead to novel therapies targeting the progression of ALD.

A cohort of HCV patients with normal or near-normal aminotransferases (N = 128) underwent a liver biopsy as part of diagnostic work-up. None admitted to exceed low-risk alcohol consumption; most (90/128, 70%) described themselves as teetotalers. They received advice on abstaining from alcohol, but not antiviral treatment. After a median follow-up period of 10 years, all underwent a second liver biopsy. HRV allele frequencies were compared with those of a group of healthy blood donors (N = 128) and related to liver histology.

HRV allele frequencies were 0.19 in patients and 0.16 in controls (p = 0.182). In the subgroup of patients who admittedly had consumed alcohol, 20/38 (53%) carried HRV, in comparison with 27/90 patients (30%) who had denied to consume alcohol (p = 0.026 by Fisher's exact test). Carriage of HRV was associated with higher histologic grade (p = 0.002) and stage (p = 0.009) at the final biopsy. At multivariate analysis, among a set of variables also including viral genotype, viral load, body mass index, gender, and history of alcohol consumption, only age (OR = 1.06, 95% CI 1.02 to 1.11) and HRV (OR = 3.13, 95% CI 1.28 to 7.68) were independent predictors of significant fibrosis at the end of follow-up.

The link between HRV carriage and histologic outcome in a subgroup of HCV patients at low risk of progression underlines the need for intense scrutiny of alcohol habits in hepatitis C.

Subjects from Vienna, Austria (n = 323) were genotyped, and single nucleotide polymorphisms (1,152) encompassing the genetic locations of the 9 ADCY genes were examined. The Vienna cohort contained alcohol-dependent subjects differentiated using the Lesch Alcoholism Typology. In this typology, subjects are segregated into 4 types. Type III alcoholism is distinguished by co-occurrence of symptoms of depression and by affecting predominantly females.

We identified 4 haplotypes associated with the phenotype of Type III alcoholism in females. One haplotype was in a genomic area in proximity to ADCY2, but actually within a lincRNA gene, 2 haplotypes were within ADCY5, and 1 haplotype was within the coding region of ADCY8. Three of the 4 haplotypes contributed independently to Type III alcoholism and together generated a positive predictive value of 72% and a negative predictive value of 78% for distinguishing women with a Lesch Type III diagnosis versus women designated as Type I or II alcoholics.

Polymorphisms in ADCY8 and ADCY5 and within a lincRNA are associated with an alcohol-dependent phenotype in females, which is distinguished by comorbid signs of depression. Each of these genetic locations can rationally contribute to the polygenic etiology of the alcoholism/depression phenotype, and the use of these genetic markers may aid in choosing appropriate and beneficial treatment strategies.

Data were from 3,983 male twins and 2,630 female twins who had ever used alcohol, interviewed in the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Mastery was measured by a 6-item scale. Lifetime diagnosis of alcohol dependence was based on DSM-IV criteria assessed in a structured diagnostic interview. Univariate analyses modeled the relative contributions of genetic and environmental factors to mastery and alcohol dependence using Mx software. Bivariate Cholesky models were fit to the mastery and alcohol dependence raw data.

In the best-fitting model of mastery, genetic factors accounted for about 33% of the observed variance. Nonshared environmental factors, including random measurement error, accounted for the remaining 67%. Fifty-six percent of the variance in liability to alcohol dependence was genetic, and the other 44% was explained by the nonshared environment. The phenotypic polychoric correlation between mastery and alcohol dependence of −0.18 was primarily (67% in the best-fitting model) explained by genes common to both low mastery and alcohol dependence; the rest was explained by nonshared environmental factors.

The findings indicate that genetic risk for alcohol dependence overlaps with genetic factors that influence sense of mastery. Key challenges for future research are to identify the genes that influence mastery and alcohol dependence, as well as the environmental pathways by which they come to be linked.

Mouse lung fibroblasts were stimulated with EtOH (60 mM) or acetylcholine (100 to 500 μM) and evaluated for the expression of fibronectin and nAChRs. Inhibitors to nAChRs or the antioxidant N-acetyl cysteine (NAC) were used to assess changes in fibronectin expression. Animals exposed to EtOH for up to 6 weeks were used to evaluate the expression of nAChRs in vivo.

First, in EtOH-treated fibroblasts, we observed increased expression of α4 and α9 nAChR subunits. Second, we found that acetylcholine, a natural ligand for nAChRs, mimicked the effects of EtOH. Dihydro-β-erythroidin hydrobromide, a competitive inhibitor of α4 nAChR, blocked the increase in fibronectin expression and cell proliferation. Furthermore, EtOH-induced fibronectin expression was inhibited in cells silenced for α4 nAChR. However, EtOH-treated cells showed increased α-bungarotoxin binding suggesting that α4 nAChR mediates the effects of EtOH via a ligand-independent pathway. Knowing there are several important cysteine residues near the ligand-binding site of α4 nAChRs, we tested the antioxidant NAC and found that it too blocked the induction of fibronectin expression by EtOH. Also, fibroblasts exposed to oxidant stress showed increased fibronectin expression that was blocked with α-bungarotoxin. Finally, we showed increased expression of α4 nAChRs in the lung tissue of mice and rats exposed to EtOH suggesting a role for these receptors in vivo.

Altogether, our observations suggest that α4 nAChRs serve as sensors for EtOH-induced oxidant stress in lung fibroblasts, thereby revealing a new mechanism by which EtOH may affect lung cells and tissue remodeling and pointing to nAChRs as potential targets for intervention.

Cerebral cortical volume, thickness, and surface area were characterized by ex vivo MRI in Long-Evans rat pups born from dams that were EtOH-treated, maltose/dextrin-treated, or untreated throughout gestation at 6 developmental time points (postnatal day [P] 0, P3, P6, P11, P19, and P60).

Brain volume, isocortical volume, isocortical thickness, and isocortical surface area were all demonstrated to be reduced following prenatal exposure to EtOH. Significant differences among the treatment groups were observed throughout the range of time points studied, allowing for a comprehensive view of FASD influenced MRI outcomes throughout development. Isocortical surface area and isocortical thickness results contributed independent information important to interpreting effects of prenatal EtOH exposure on cerebral cortical development. Additionally, regional patterns in cortical thickness differences suggested primary sensory areas were particularly vulnerable to gestational EtOH exposure.

Structural MRI measurements were in accordance with previous histological studies performed in animal models of FASD. In addition to establishing a summary of MRI outcomes throughout development in FASD, this research suggests that MRI techniques are sufficiently sensitive to detect neuroanatomical effects of fetal EtOH exposure on development of the cerebral cortex during the period of time corresponding to late gestation in humans. Importantly, this research provides a link between animal histological data and human MRI data.

We took advantage of organotypic cultures (explants) of the hypothalamo-neurohypophysial system (HNS) to extend our analysis of molecular tolerance to 2 classes of the VGCC. The isolated HNS explant allows much finer temporal resolution of molecular tolerance than do voluntary drinking paradigms. After exposure of the HNS explant to alcohol, terminals are isolated by mechanical treatment and plated in a dish. Patch clamp recording techniques are used to obtain VGCC currents, and immunohistochemistry is used to determine VGCC distribution. A release assay is used to provide functional readout of AVP release.

We show that even a brief, 1-hour exposure to a clinically relevant concentration of alcohol is sufficient to evoke similar changes to those observed after several weeks of exposure. Acute ethanol (EtOH) exposure inhibits high K⁺-induced AVP release from naïve terminals. However, terminals pre-exposed to 20 mM EtOH for 1 hour become tolerant to EtOH, and subsequent exposure has significantly less effect on high K⁺-induced AVP release. Electrophysiological recordings indicate that among different types of VGCCs present in the neuronal terminal, the L-type is the most affected by alcohol. The current density of L-type current is significantly increased (approximately 50%), while its responsiveness to alcohol is significantly diminished (approximately 50%), after brief alcohol exposure. Fluorescent imaging results were consistent with the electrophysiology and suggest that the increased current density of VGCCs after brief exposure is attributable to combined synthesis of 1.2 and 1.3 subtypes of the L-type VGCC and redistribution of channel protein into terminal plasma membrane.

These data indicate that a brief alcohol exposure affects subsequent alcohol sensitivity of VGCCs and neuropeptide release from presynaptic terminals.

Participants included healthy older (aged 50 to 67; n = 20; 9 men) and younger (aged 25 to 35; n = 12; 5 men) moderate drinkers. Participants received either a moderate dose of alcohol (breath alcohol concentration ∼50 mg/dl) or a placebo beverage. Following absorption, the task was administered and neurophysiological measures were obtained. P3 amplitude and latency were separately subjected to ANOVA across cue conditions using age and dose as independent variables.

As predicted, P3 amplitude in older adults was significantly lower than in younger adults across cue conditions. An age by alcohol interaction was detected, revealing that older adults receiving alcohol showed lower P3 amplitudes than any other group. An age effect for P3 latency was found, with older adults having longer latencies than their younger counterparts. A significant age by alcohol interaction for P3 latency was detected, revealing that older adults receiving alcohol displayed delayed P3 latencies relative to older adults receiving placebo. In contrast, younger adults receiving alcohol had reduced latency compared to those receiving placebo, although this effect did not reach significance.

Results suggest that older adults demonstrated alcohol-related shifts in P3 characteristics during an intentional attention task, whereas younger adults failed to demonstrate this pattern.

Adolescent male rhesus monkeys (n = 10) were trained to respond to visual stimuli on touch-sensitive LCD panels controlled by the nonhuman primate version of CANTAB software. Discrimination and reversal learning tasks were subsequently assessed after monkeys were allowed to consume varying amounts of ethanol (EtOH) in a flavored vehicle (vehicle only, up to 0.5 g/kg EtOH, up to 1.0 g/kg EtOH, and up to 1.5 g/kg EtOH).

Acute exposure to EtOH reduced perseverance, increased response accuracy, and reduced errors during reversal learning when the task was completed within 90 minutes of EtOH consumption. No reduction in reversal errors was observed when EtOH was consumed 3 or 24 hours prior to reversal learning. EtOH only impaired discrimination learning when monkeys had very little previous EtOH exposure.

The temporal relationship between EtOH consumption and reversal learning was consistent with selective EtOH-induced impairment of retrieval, but not storage, processes. This was evidenced by diminished perseverance on the previously correct stimulus leading to decreased errors to criterion.

Male adolescent (PND = 28 to 30) and adult (PND = 70) C57BL/6J mice were allowed to consume EtOH in a 2-bottle choice paradigm (15% EtOH vs. water) for 3 weeks (Baseline drinking, Test 1, and Test 2), which were interspersed with 2 cycles (Cycles I and II) of chronic EtOH vapor or air inhalation (16 hours) and withdrawal (8 hours). BECs were determined during both cycles.

Chronic EtOH exposure led to increased EtOH intake during Test 1 and Test 2 in both adolescent and adult mice compared with air-exposed controls, and no differences between age groups were observed. During Cycle I adult mice showed higher BECs compared with adolescents. During Cycle II, BECs were lower in adult mice as compared to Cycle I, and BECs in adolescent mice did not change between the 2 cycles.

Chronic EtOH exposure followed by withdrawal periods increases EtOH consumption similarly in both adolescent and adult mice, despite differences in BECs.

Alcohol was administered starting 3 months before SIVmac251 inoculation to the end of the study via an indwelling intragastric catheter to achieve a plasma alcohol concentration of 50 to 60 mM. Control animals received isocaloric sucrose. Four months after SIV infection, the right lung was inoculated with 2 × 10⁶ CFU S. pneumoniae.

Leukocyte recruitment into the lung, pulmonary bacterial clearance, and clinical course were similar between EtOH and control groups. While plasma SIV viral load was similar between groups postpneumonia, chronic EtOH-fed macaques showed a prolonged increase in SIV RNA in bronchoalveolar lavage fluid. Alveolar macrophages isolated from EtOH-fed macaques 1 day post-pneumonia showed greater nuclear factor kappa beta (NF-κB) activation.

This study indicates that chronic EtOH feeding results in enhanced local, but not systemic, SIV replication following pneumococcal pneumonia. Increased NF-κB activity in the setting of chronic EtOH ingestion may play a mechanistic role in this observation.

Participants were a convenience sample of adults who drink alcohol or who pour drinks for other people (n = 283, 54% women) at 6 sites in South East England. The survey was face to face and comprised a self-completion questionnaire and pouring task. Estimation accuracy, categorised as correct (±0.5 units), underestimate (>0.5 units), or overestimate (>0.5 units) was the main outcome.

The mean number of units poured was 1.90 (SD 0.80; n = 264) for wine and 1.93 (SD 0.78; n = 201) for spirits. The amount of alcohol in a self-defined usual glass was estimated in 440 glasses (248 wine and 192 spirits). Overestimation took place in 42% glasses of spirit poured and 29% glasses of wine poured, and underestimation in 17 and 19%, respectively. Multinomial logistic regression found volume poured to be significantly associated with underestimating both wines and spirits, and additionally for wine only, belonging to a non-white ethnic group and being unemployed or retired. Not having a university degree was significantly associated with overestimating both drink types.

This study is the first in the general population and did not identify systematic underestimation of the amount of alcohol in a self-defined usual glass. Underestimation is significantly associated with volume poured for both drink types; therefore, advocating pouring smaller glasses could reduce underestimation of alcohol consumption.

The prevalence of 5 types of childhood trauma—emotional abuse, sexual abuse, physical abuse, emotional neglect, and physical neglect—was assessed in treatment-seeking alcohol-dependent patients (n = 280) and healthy controls (n = 137) using the Childhood Trauma Questionnaire. Multiple mediation analyses were used to model associations between childhood trauma measures and alcohol-related outcomes, primarily the severity of AD in the alcohol-dependent sample.

Childhood trauma was significantly more prevalent and more severe in the alcohol-dependent subjects. In addition, childhood trauma was found to influence AD severity, an effect that was mediated by neuroticism. When individual trauma types were examined, emotional abuse was found to be the primary predictor of AD severity, both directly and through the mediating effects of the impulsivity subfacet of neuroticism. Physical abuse also had a moderate direct effect on AD severity. Mediation analysis did not reveal any association between childhood trauma and Alcohol Use Disorders Identification Test score in the nondependent control sample.

Childhood trauma is highly prevalent in treatment-seeking alcoholics and may play a significant role in the development and severity of AD through an internalizing pathway involving negative affect. Our findings suggest that alcoholics with a history of childhood emotional abuse may be particularly vulnerable to severe dependence.

Data were collected via a telephone survey of parents in 50 cities in California, resulting in 2,163 respondents who reported drinking in the past year. Child physical abuse and corporal punishment were measured using the Conflict Tactics Scale, Parent–Child version. Drinking behaviors were measured using continued drinking measures. Data were analyzed using zero-inflated Poisson models.

Drinking at homes, parties, or bars more frequently was related to greater frequencies of physically abusive parenting practices. The use of greater amounts of alcohol in association with drinking at bars appeared to increase risks of corporal punishment, a dose–response effect. Dose–response relationships were not found for drinking at homes or parties or drinking at bars for physical abuse nor for drinking at home and parties for corporal punishment.

Frequencies of using drinking venues, particularly bars and home or parties, are associated with greater use of abusive parenting practices. These findings suggest that a parent's routine drinking activities place children at different risks of being physically abused. They also suggest that interventions that take into account parents’ alcohol use at drinking venues are an important avenue for secondary prevention efforts.

Experts in the field of substance use disorder classification carried out standardized appraisal of 4 DSM-IV diagnostic criteria for alcohol abuse/dependence (hazard, tolerance, larger/longer, quit/cut down). Cross-sectional surveys of 100 young adult drinkers aged 18 to 24 were carried out. All participants were administered a structured diagnostic interview as well as a structured cognitive interview. The cognitive interviews were comprised of a set of predetermined and standardized probe questions designed to shed light on young adults' understanding of interview questions designed to tap the AUD diagnostic criteria. Answers to the cognitive interview probe questions were summarized across the total sample and, where appropriate, comparisons were made between those who endorsed the diagnostic criterion and those who did not.

Results showed that there were substantial inconsistencies in young adults' interpretations of survey questions reflecting impaired control over alcohol. Interpretations of questions designed to measure tolerance to the effects of alcohol and use of alcohol in hazardous situations were largely understood as intended by the architects of DSM.

Survey questions designed to tap compulsive patterns of alcohol use require close attention to ensure they reflect the intentions of the DSM diagnostic criteria for AUD.

The feasibility of collecting an additional DBS card during routine newborn screening and the background prevalence of PAE were evaluated in a de-identified sample of newborn children delivered at the University of New Mexico Hospital. Electronic orders to collect DBS cards from newborns who continue to bleed after the routine newborn screen, glucose, or hematocrit testing were initiated for all infants delivered during a 4-week time frame. Specimens were sent to a contract laboratory for PEth analysis by liquid chromatography–tandem mass spectrometry. A cost analysis was conducted to compare the cost of PAE screening by PEth in DBS versus PEth in conventional blood specimens and by meconium fatty acid ethyl esters.

From 230 collected cards, 201 (87.4%) had at least 1 full blood spot (amount sufficient for PEth analysis), and 6.5% had PEth >20 ng/ml indicative of potential PAE in late pregnancy. PAE screening by PEth in DBS is logistically simpler and less expensive compared with 2 other screening approaches.

These results indicate that screening for PAE in DBS cards is a feasible procedure and that a majority of infants have enough blood after the routine heel prick to fill an additional card. Moreover, screening by PEth analysis from DBS cards is cost-efficient. The acceptability of such screening by parents and corresponding ethical issues remain to be investigated.

We employed a sample of 4,281 same-sex twins from the Australian Twin Register to examine whether (i) large sibship size facilitates earlier age at first drink (AFD) and age at first intoxication (AFI) in males and females, (ii) having many older brothers predicts earlier ages of AFD and AFI in males, and (iii) having many older brothers results in later AFD and AFI in females. We tested whether effects were moderated by parental divorce and alcohol misuse and mediated by familial religion.

Sibling effects were minimal before accounting for family context. However, when parental divorce and excessive parental drinking were included as moderators, sibling effects were significantly amplified among individuals from homes of divorce, and effects were strongest when siblings were close in age.

Strong close in age older sibling effects indicate that proximal sibling attitudes and behaviors about alcohol likely interact with structural factors to influence younger siblings’ drinking. Sibship factors were much more influential in one population (individuals from homes of divorce) than another (respondents with a parental history of excessive drinking), suggesting that sibling effects vary depending on the type of co-occurring familial risk. Prevention efforts performed at the family level, and introduced before first use of alcohol, are likely to delay drinking initiation and help prevent future alcohol problems.

Fourteen KS, 15 AL, and 15 CS were submitted to 40 trials (4 daily learning sessions) of the Tower of Toronto task (disk-transfer task similar to the tower of Hanoi task) as well as episodic and working memory tasks.

The 10 KS who were able to perform the cognitive procedural learning task obtained lower results than both CS and AL. The cognitive phase was longer in the Korsakoff's syndrome group than in the other 2 groups but did not differ between the 3 groups any more when episodic memory abilities were controlled.

Our results indicate that KS have impaired cognitive procedural learning abilities compared with both AL and CS. Episodic memory deficits observed in KS result in a delayed transition from the cognitive learning phase to more advanced learning phases and, as a consequence, in an absence of automation of the procedure within 40 trials.

The solution (EtOH or saccharin) was always available following 5 responses. Presentation of flashing stimulus lights indicated food delivery followed 150 responses and resulted in responding predominately for the solution (84 to 86% of total responses). Presentation of solid stimulus lights indicated food delivery followed 5 responses and resulted in responding predominately for food (1 to 3% of total responses were for the solution). Rats were exposed to solid light conditions for 0, 1, 2, 4, or 16 consecutive sessions before being re-exposed to the flashing stimulus lights in extinction.

Responding for either solution resumed when rats were re-exposed to the flashing stimulus lights (associated with solution-predominate responding). However, more responses occurred on the food lever with longer recent histories of responding for food instead of the solution.

These results suggest that the longer alternative behavior replaces drinking, the more that attention to stimuli associated with drinking decreases. These results are consistent with the notion that the risk of relapse declines with longer periods of recovery because alternative behavior comes to predominate even in the presence of stimuli associated with drinking.

Study participants were 644 undergraduate students (67.2% female; 87.2% Caucasian) who completed a series of online questionnaires as a part of a larger longitudinal study on sleep and substance use. The mean age of participants was 23.58 (SD = 6.861).

Students with a higher autonomy orientation were more likely than their counterparts to report that they did not drink in the last 6 months. In contrast, students with a higher controlled orientation were less likely to report that they did not drink. Among those who drank in the last 6 months, effortful control significantly mediated the effects of autonomy orientation and controlled orientation on frequency of alcohol use within that time frame. Autonomy orientation positively predicted effortful control, which was associated with a decrease in the expected frequency of drinking. In contrast, controlled orientation negatively predicted effortful control, which was associated with an increase in the expected frequency of drinking. Controlled orientation also significantly predicted the presence of alcohol-related problems and illicit drug use.

Intervention and prevention programs on college drinking could incorporate education about strategies for self-control, including strategies for withstanding peer pressure and diverting one's attention to activities unrelated to substance use. Focusing on strategies of self-control may be a useful starting point for a more in-depth discussion about the motivations, values, and psychological needs satisfaction that are associated with drinking and other drug use.

Pair-housed Sprague-Dawley adolescent (postnatal day [P] 28 to 42) rats of both sexes were given single bottle access to 1 of 3 solutions in their home cages—10% EtOH in “supersac” (0.125% saccharin and 3% sucrose) (EtOH/SS), supersac without EtOH (SS), or water—for 30 minutes every other day for a total of 8 drinking days or were left nonmanipulated (NM). Animals were NM thereafter until adulthood (P70) at which time they were given 1-bottle, 30 minute limited access tests with 20% EtOH every other day (Exp 1), 10% EtOH in SS (Exp 2), or SS without EtOH (Exp 3).

Adolescent EtOH/SS exposure increased adulthood consumption of EtOH/SS (Exp 2), but not 20% unsweetened EtOH (Exp 1) or SS (Exp 3), with this increase most pronounced at the beginning of the 8 intake day procedure. Access to SS (without EtOH) during adolescence produced an analogous effect, with increased adult SS consumption during the first 2 intake days, but no increases in either of the EtOH test solutions.

Solution-specific increases in adulthood intake after adolescent exposure are most likely associated with solution acceptance due to familiarity. This is an important consideration for future intake studies assessing the influence of EtOH exposure during adolescence on intake of EtOH in adulthood.

One hundred and seventy-eight participants (mean age = 21.87, SD = 1.23; 57% African American) who were moderate to heavy social drinkers completed an alcohol administration study in a laboratory setting, receiving a moderate dose of alcohol (0.72 g/kg alcohol for men, 0.65 g/kg for women). Acute alcohol response was measured at 8 time points (i.e., baseline, 15, 30, 45, 60, 90, 120, and 150 minutes).

Latent growth curve models showed that African Americans experienced sharper increases in stimulation on the ascending limb compared to European Americans. African American women experienced sharper increases in sedation on the ascending limb compared to European American women. Change in sedation on the ascending limb was associated with past month drinking behavior. Stimulation on the ascending limb was related to alcohol problems for African Americans but not European Americans.

We found differences in response to alcohol across racial groups: African Americans showed a stronger response to alcohol. Future studies are needed to incorporate response to alcohol into a larger model of African American alcohol use.

A multivariate meta-analysis of naltrexone pharmacotherapy trials for alcohol use disorders was conducted. All analyses simultaneously modeled ESs on outcomes of percent days abstinent and relapse to heavy drinking. Potential moderators of medication effects that were examined included publication year, multicenter design (vs. single site), placebo run-in period, and placebo group improvement.

Statistically significant between-group differences on percent days abstinent (the inverse of percent days drinking) and relapse to heavy drinking favored naltrexone over placebo. Year of publication was a significant moderator for both outcomes, with more recent trials having smaller ESs. Neither multi- versus single-site study, the interaction between multi- versus single-site study and year of publication, nor placebo run-in period was a significant moderator of naltrexone effects. Although placebo group improvement was modestly associated with smaller between-group naltrexone versus placebo ESs, only 21 studies provided usable information on placebo group improvement. Within those studies, there was no relationship between naltrexone ESs and time, so placebo group improvement was not examined as a moderator of that relationship.

Naltrexone ESs have attenuated over time. Moderators that explain why effects have been decreasing remain to be determined.